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Torreggiani M, Fois A, Santagati G, De Marco O, Bedogni S, Cacciatori N, Ruotolo C, Magli A, Piccoli GB. Severe maternal undernutrition during pregnancy and its long-term effects on the offspring health, with a focus on kidney health. Pediatr Nephrol 2025; 40:1853-1862. [PMID: 39601824 DOI: 10.1007/s00467-024-06552-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/24/2024] [Accepted: 10/02/2024] [Indexed: 11/29/2024]
Abstract
Maternal undernutrition during pregnancy is associated with adverse effects in the offspring during adulthood and contributes to the risk of developing a number of chronic diseases. Historical events, such as famines, allow us to study the effects that food deprivation in utero has on the offspring's health. In particular, the Dutch Hunger Winter (1944-1945) and the Great Chinese Famine (1959-1961) have been extensively analysed, and it has been shown that prenatal exposure to starvation increases the risk of cardiometabolic, mental and kidney disease in adult life. More importantly, the risk can be transmitted to future generations. However, not all studies agree on the thresholds of risk of exposed subjects or on the timing of starvation during foetal life that could be held responsible for these deleterious lifelong consequences. Gender differences complicate the picture. In this narrative review, we discuss similarities and differences between the two famines and compare the available data, seeking to determine what can be learned from these tragedies.
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Affiliation(s)
- Massimo Torreggiani
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Antioco Fois
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Giulia Santagati
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Oriana De Marco
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Stella Bedogni
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Nicolò Cacciatori
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Chiara Ruotolo
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Anna Magli
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France
| | - Giorgina Barbara Piccoli
- Néphrologie et Dialyse, Centre Hospitalier Le Mans, 194 Avenue Rubillard, 72037, Le Mans, France.
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Chevalley T, Dübi M, Fumeaux L, Merli MS, Sarre A, Schaer N, Simeoni U, Yzydorczyk C. Sexual Dimorphism in Cardiometabolic Diseases: From Development to Senescence and Therapeutic Approaches. Cells 2025; 14:467. [PMID: 40136716 PMCID: PMC11941476 DOI: 10.3390/cells14060467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/03/2025] [Accepted: 03/14/2025] [Indexed: 03/27/2025] Open
Abstract
The global incidence and prevalence of cardiometabolic disorders have risen significantly in recent years. Although lifestyle choices in adulthood play a crucial role in the development of these conditions, it is well established that events occurring early in life can have an important effect. Recent research on cardiometabolic diseases has highlighted the influence of sexual dimorphism on risk factors, underlying mechanisms, and response to therapies. In this narrative review, we summarize the current understanding of sexual dimorphism in cardiovascular and metabolic diseases in the general population and within the framework of the Developmental Origins of Health and Disease (DOHaD) concept. We explore key risk factors and mechanisms, including the influence of genetic and epigenetic factors, placental and embryonic development, maternal nutrition, sex hormones, energy metabolism, microbiota, oxidative stress, cell death, inflammation, endothelial dysfunction, circadian rhythm, and lifestyle factors. Finally, we discuss some of the main therapeutic approaches, responses to which may be influenced by sexual dimorphism, such as antihypertensive and cardiovascular treatments, oxidative stress management, nutrition, cell therapies, and hormone replacement therapy.
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Affiliation(s)
| | | | | | | | | | | | | | - Catherine Yzydorczyk
- Developmental Origins of Health and Disease (DOHaD) Laboratory, Division of Pediatrics, Department Woman-Mother-Child, Lausanne University Hospital, University of Lausanne, 1011 Lausanne, Switzerland; (T.C.); (M.D.); (L.F.); (M.S.M.); (A.S.); (N.S.)
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3
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Wiegersma AM, Roseboom TJ, de Rooij SR. Women exposed to famine in early gestation have increased mortality up to age 76 years. Paediatr Perinat Epidemiol 2025; 39:236-241. [PMID: 39351622 PMCID: PMC11997240 DOI: 10.1111/ppe.13131] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/18/2024] [Accepted: 09/21/2024] [Indexed: 04/16/2025]
Abstract
BACKGROUND We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64. OBJECTIVES Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately. METHODS We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944-1945 Dutch famine. We compared overall and cause-specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression. RESULTS In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups. CONCLUSION This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women.
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Affiliation(s)
- Aline Marileen Wiegersma
- Epidemiology and Data ScienceAmsterdam UMC Location University of AmsterdamAmsterdamThe Netherlands
- Health Behaviors & Chronic Diseases, Aging & Later LifeAmsterdam Public Health Research InstituteAmsterdamThe Netherlands
- Amsterdam Reproduction and DevelopmentAmsterdamThe Netherlands
| | - Tessa J. Roseboom
- Epidemiology and Data ScienceAmsterdam UMC Location University of AmsterdamAmsterdamThe Netherlands
- Health Behaviors & Chronic Diseases, Aging & Later LifeAmsterdam Public Health Research InstituteAmsterdamThe Netherlands
- Amsterdam Reproduction and DevelopmentAmsterdamThe Netherlands
- Obstetrics and GynaecologyAmsterdam UMC Location University of AmsterdamAmsterdamThe Netherlands
| | - Susanne R. de Rooij
- Epidemiology and Data ScienceAmsterdam UMC Location University of AmsterdamAmsterdamThe Netherlands
- Health Behaviors & Chronic Diseases, Aging & Later LifeAmsterdam Public Health Research InstituteAmsterdamThe Netherlands
- Amsterdam Reproduction and DevelopmentAmsterdamThe Netherlands
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Charney E, Darity W, Hubbard L. How epigenetic inheritance fails to explain the Black-White health gap. Soc Sci Med 2025; 366:117697. [PMID: 39827685 DOI: 10.1016/j.socscimed.2025.117697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 12/19/2024] [Accepted: 01/10/2025] [Indexed: 01/22/2025]
Abstract
Slavery, legal segregation, and ongoing discrimination have exacted an unfathomable toll on the black population in the United States, particularly with respect to the impact on health outcomes. In recent years, various researchers and activists have suggested that racial disparities in the modern era can be attributed directly to the trauma of slavery, postulating that these unspeakable traumas led to epigenetic changes in slaves-changes that have since been passed down to subsequent generations. Investigating those claims in this paper, we comprise a review of previous literature that considers the potential for transgenerational epigenetic transmission of trauma in humans. However, we find that there is little evidence to indicate the presence of transgenerational epigenetic transmission of trauma in humans. We find no prior evidence that supports (or is relevant to) the notion that the black-white health gap stems from the inherited trauma of slavery. We conclude that, given the ongoing traumas black Americans are exposed to in modern America, it is much more likely that present-day racial health disparities are due to more direct and current mechanisms than transgenerational transmission of slavery-era trauma.
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Affiliation(s)
| | - William Darity
- Samuel DuBois Cook Center on Social Equity at Duke University, Durham, NC, USA.
| | - Lucas Hubbard
- Samuel DuBois Cook Center on Social Equity at Duke University, Durham, NC, USA.
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Bozack AK, Trasande L. Prenatal chemical exposures and the methylome: current evidence and opportunities for environmental epigenetics. Epigenomics 2024; 16:1443-1451. [PMID: 39539208 PMCID: PMC11622816 DOI: 10.1080/17501911.2024.2426441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 10/29/2024] [Indexed: 11/16/2024] Open
Abstract
Exposure to pollutants and chemicals during critical developmental periods in early life can impact health and disease risk across the life course. Research in environmental epigenetics has provided increasing evidence that prenatal exposures affect epigenetic markers, particularly DNA methylation. In this article, we discuss the role of DNA methylation in early life programming and review evidence linking the intrauterine environment to epigenetic modifications, with a focus on exposure to tobacco smoke, metals, and endocrine-disrupting chemicals. We also discuss challenges and novel approaches in environmental epigenetic research and explore the potential of epigenetic biomarkers in studies of pediatric populations as indicators of exposure and disease risk. Overall, we aim to highlight how advancements in environmental epigenetics may transform our understanding of early-life exposures and inform new approaches for supporting long-term health.
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Affiliation(s)
- Anne K. Bozack
- Department of Epidemiology and Population Health, Stanford School of Medicine, Palo Alto, CA, USA
| | - Leonardo Trasande
- Department of Pediatrics and Department of Population Health, New York University School of Medicine, New York, NY, USA
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Wells JCK, Williams FL, Desoye G. Reverse-engineering the Venus figurines: An eco-life-course hypothesis for the aetiology of obesity in the Palaeolithic. Evol Med Public Health 2024; 12:262-276. [PMID: 39711972 PMCID: PMC11659884 DOI: 10.1093/emph/eoae031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 10/28/2024] [Indexed: 12/24/2024] Open
Abstract
Evolutionary perspectives on obesity have been dominated by genetic frameworks, but plastic responses are also central to its aetiology. While often considered a relatively modern phenomenon, obesity was recorded during the Palaeolithic through small statuettes of the female form (Venus figurines). Even if the phenotype was rare, these statuettes indicate that some women achieved large body sizes during the last glacial maximum, a period of nutritional stress. To explore this paradox, we develop an eco-life-course conceptual framework that integrates the effects of dietary transitions with intergenerational biological mechanisms. We assume that Palaeolithic populations exposed to glaciations had high lean mass and high dietary protein requirements. We draw on the protein leverage hypothesis, which posits that low-protein diets drive overconsumption of energy to satisfy protein needs. We review evidence for an increasing contribution of plant foods to diets as the last glacial maximum occurred, assumed to reduce dietary protein content. We consider physiological mechanisms through which maternal overweight impacts the obesity susceptibility of the offspring during pregnancy. Integrating this evidence, we suggest that the last glacial maximum decreased dietary protein content and drove protein leverage, increasing body weight in a process that amplified across generations. Through the interaction of these mechanisms with environmental change, obesity could have developed among women with susceptible genotypes, reflecting broader trade-offs between linear growth and adiposity and shifts in the population distribution of weight. Our approach may stimulate bioarchaeologists and paleoanthropologists to examine paleo-obesity in greater detail and to draw upon the tenets of human biology to interpret evidence.
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Affiliation(s)
- Jonathan C K Wells
- Population, Policy and Practice Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, UK
| | | | - Gernot Desoye
- Department of Obstetrics and Gynaecology, Medical University of Graz, Graz, Austria
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Hunt KJ, Wen CC, Neelon B, Wilson DA, Mateus J, Pearce J, Chundru K, Simpson S, Korte JE, Florez H, Malek AM. Increasing Prevalence of Diagnosed Gestational Diabetes in South Carolina: 2015-2021. J Womens Health (Larchmt) 2024; 33:1518-1527. [PMID: 39229709 PMCID: PMC11698680 DOI: 10.1089/jwh.2023.1042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2024] Open
Abstract
Objective: To examine trends with a focus on racial and ethnic disparities in reported gestational diabetes mellitus (GDM) and related outcomes (macrosomia, large for gestational age infants) before and during the COVID-19 pandemic in South Carolina (SC). Methods: A retrospective cohort study of pregnancies resulting in livebirths from 2015 through 2021 was conducted in SC. Statewide maternal hospital and emergency department discharge codes were linked to birth certificate data. GDM was defined by ICD-9-CM (i.e., 648.01-648.02, 648.81-648.82) or ICD-10-CM codes (i.e., O24.4, O24.1, O24.9), or indication of GDM on the birth certificate without evidence of diabetes outside pregnancy (ICD-9-CM: 250.xx; ICD-10-CM: E10, E11, O24.0, O24.1, O24.3). Results: Our study included 194,777 non-Hispanic White (White), 108,165 non-Hispanic Black (Black), 25,556 Hispanic, and 16,344 other race-ethnic group pregnancies. The relative risk for GDM associated with a 1-year increase was 1.01 (95% confidence interval [CI]: 1.01-1.02) before the pandemic and 1.12 (1.09-1.14) during the pandemic. While there were race-ethnic differences in the prevalence of GDM, increasing trends were similar across all race-ethnic groups before and during the pandemic. From quarter 1, 2020, to quarter 4, 2021, the prevalence of reported GDM increased from 8.92% to 10.85% in White, from 8.04% to 9.78% in Black, from 11.2% to 13.65% in Hispanic, and from 13.3% to 16.16% in other race-ethnic women. Conclusion: An increasing prevalence of diagnosed GDM was reported during the COVID-19 pandemic. Future studies are needed to understand the mechanisms underlying increasing trends, to develop interventions, and to determine whether the increasing trend continues in subsequent years.
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Affiliation(s)
- Kelly J. Hunt
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
- Health Equity and Rural Outreach Innovation Center, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
| | - Chun-Che Wen
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Brian Neelon
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
- Health Equity and Rural Outreach Innovation Center, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
| | - Dulaney A. Wilson
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Julio Mateus
- Maternal-Fetal Medicine Division, Department of Obstetrics & Gynecology, Atrium Health, Charlotte, North Carolina, USA
| | - John Pearce
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Kalyan Chundru
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Sarah Simpson
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Jeffrey E. Korte
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Hermes Florez
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
- Health Equity and Rural Outreach Innovation Center, Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina, USA
| | - Angela M. Malek
- Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
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Taeubert MJ, Kuipers TB, Zhou J, Li C, Wang S, Wang T, Tobi EW, Belsky DW, Lumey LH, Heijmans BT. Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases. BMC Med 2024; 22:309. [PMID: 39075494 PMCID: PMC11287851 DOI: 10.1186/s12916-024-03529-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/12/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type 2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to identify the metabolic changes that are associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and subsequently assess their link to disease. METHODS NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. RESULTS Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3 × 10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type 2 diabetes from the UK Biobank (r = 0.77, p = 3 × 10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1 × 10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2 × 10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. CONCLUSIONS Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.
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Affiliation(s)
- M Jazmin Taeubert
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Thomas B Kuipers
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Jiayi Zhou
- Butler Columbia Aging Center, Columbia University, New York, NY, USA
| | - Chihua Li
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
- Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA
- State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao SAR, China
| | - Shuang Wang
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Tian Wang
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Elmar W Tobi
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Daniel W Belsky
- Butler Columbia Aging Center, Columbia University, New York, NY, USA
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - L H Lumey
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Bastiaan T Heijmans
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
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Kearns ML, Reynolds CM. Developmentally programmed obesity: Is there a role for anti-inflammatory nutritional strategies? Exp Physiol 2024; 109:633-646. [PMID: 38031876 PMCID: PMC11061634 DOI: 10.1113/ep091209] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 11/17/2023] [Indexed: 12/01/2023]
Abstract
Pregnancy represents a period of immense maternal physiological adaptation, with progressive increases in lipid storage potential and insulin resistance to support fetal/placental growth. This requires significant change in the adipose tissue. Women living with obesity/overweight are more susceptible to these changes causing complications such as gestational diabetes. This is particularly worrying as up to 60% of European women are living with overweight/obesity at the onset of pregnancy. Furthermore, less than 1% meet all nutrition guidelines. There is now evidence that these deep metabolic changes can result in a predisposition to metabolic disease in both the mother and child in later life. Health and nutrition status during this period therefore represents a window to future health. This period offers a valuable opportunity for intervention to prevent the negative consequences of poor in utero environments and increases the long-term quality of life for mother and offspring. This review will examine a range of in utero factors which determine adipose tissue development, the impact of these factors on later-life obesity and metabolic health and the therapeutic value of dietary anti-inflammatory nutritional interventions during pregnancy and early life. When it comes to early life nutrition, a 'one size fits all' approach is not always appropriate. Understanding the mechanisms of adipose tissue development in response to differing nutritional strategies may be important in the context of complicated or adverse in utero environments and represents a substantial step towards a more personalised nutritional approach for the prevention of obesity, metabolic syndrome and related non-communicable diseases in future generations.
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Affiliation(s)
- Michelle L. Kearns
- Conway Institute/School of Public Health Physiotherapy and Sports Science/Institute of Food and Health/Diabetes Complications Research CentreUniversity College DublinDublin 4Ireland
| | - Clare M. Reynolds
- Conway Institute/School of Public Health Physiotherapy and Sports Science/Institute of Food and Health/Diabetes Complications Research CentreUniversity College DublinDublin 4Ireland
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10
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Taeubert MJ, Kuipers TB, Zhou J, Li C, Wang S, Wang T, Tobi EW, Belsky DW, Lumey LH, Heijmans BT. Adults prenatally exposed to the Dutch Famine exhibit a metabolic signature associated with a broad spectrum of common diseases. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.04.04.24305284. [PMID: 38633796 PMCID: PMC11023671 DOI: 10.1101/2024.04.04.24305284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/19/2024]
Abstract
Background Exposure to famine in the prenatal period is associated with an increased risk of metabolic disease, including obesity and type-2 diabetes. We employed nuclear magnetic resonance (NMR) metabolomic profiling to provide a deeper insight into the metabolic changes associated with survival of prenatal famine exposure during the Dutch Famine at the end of World War II and explore their link to disease. Methods NMR metabolomics data were generated from serum in 480 individuals prenatally exposed to famine (mean 58.8 years, 0.5 SD) and 464 controls (mean 57.9 years, 5.4 SD). We tested associations of prenatal famine exposure with levels of 168 individual metabolic biomarkers and compared the metabolic biomarker signature of famine exposure with those of 154 common diseases. Results Prenatal famine exposure was associated with higher concentrations of branched-chain amino acids ((iso)-leucine), aromatic amino acid (tyrosine), and glucose in later life (0.2-0.3 SD, p < 3x10-3). The metabolic biomarker signature of prenatal famine exposure was positively correlated to that of incident type-2 diabetes (r = 0.77, p = 3x10-27), also when re-estimating the signature of prenatal famine exposure among individuals without diabetes (r = 0.67, p = 1x10-18). Remarkably, this association extended to 115 common diseases for which signatures were available (0.3 ≤ r ≤ 0.9, p < 3.2x10-4). Correlations among metabolic signatures of famine exposure and disease outcomes were attenuated when the famine signature was adjusted for body mass index. Conclusions Prenatal famine exposure is associated with a metabolic biomarker signature that strongly resembles signatures of a diverse set of diseases, an observation that can in part be attributed to a shared involvement of obesity.
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Affiliation(s)
- M. Jazmin Taeubert
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Thomas B. Kuipers
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | - Jiayi Zhou
- Butler Columbia Aging Center, Columbia University, New York, United States
| | - Chihua Li
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States
| | - Shuang Wang
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, United States
| | - Tian Wang
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, United States
| | - Elmar W. Tobi
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Daniel W. Belsky
- Butler Columbia Aging Center, Columbia University, New York, United States
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States
| | - L. H. Lumey
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, United States
| | - Bastiaan T. Heijmans
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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11
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Conti G, Poupakis S, Ekamper P, Bijwaard GE, Lumey LH. Severe prenatal shocks and adolescent health: Evidence from the Dutch Hunger Winter. ECONOMICS AND HUMAN BIOLOGY 2024; 53:101372. [PMID: 38564976 DOI: 10.1016/j.ehb.2024.101372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 02/23/2024] [Accepted: 03/01/2024] [Indexed: 04/04/2024]
Abstract
This paper investigates health impacts at the end of adolescence of prenatal exposure to multiple shocks, by exploiting the unique natural experiment of the Dutch Hunger Winter. At the end of World War II, a famine occurred abruptly in the Western Netherlands (November 1944-May 1945), pushing the previously and subsequently well-nourished Dutch population to the brink of starvation. We link high-quality military recruits data with objective health measurements for the cohorts born in the years surrounding WWII with newly digitised historical records on calories and nutrient composition of the war rations, daily temperature, and warfare deaths. Using difference-in-differences and triple differences research designs, we first show that the cohorts exposed to the Dutch Hunger Winter since early gestation have a higher Body Mass Index and an increased probability of being obese at age 18. We then find that this effect is partly moderated by warfare exposure and a reduction in energy-adjusted protein intake. Lastly, we account for selective mortality using a copula-based approach and newly-digitised data on survival rates, and find evidence of both selection and scarring effects. These results emphasise the complexity of the mechanisms at play in studying the consequences of early conditions.
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Affiliation(s)
- Gabriella Conti
- Department of Economics and Social Research Institute, University College London, United Kingdom; Institute for Fiscal Studies, CEPR, United Kingdom; IZA, Germany.
| | - Stavros Poupakis
- Department of Economics and Finance, Brunel University London, United Kingdom
| | - Peter Ekamper
- Netherlands Interdisciplinary Demographic Institute, KNAW,, Netherlands; University of Groningen, Netherlands
| | - Govert E Bijwaard
- IZA, Germany; Netherlands Interdisciplinary Demographic Institute, KNAW,, Netherlands; University of Groningen, Netherlands
| | - L H Lumey
- Department of Epidemiology, Mailman School of Public Health, Columbia University, United States of America
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Garcia-Rizo C, Crespo-Facorro B, Oliveira C, Gómez-Revuelta M, Kirkpatrick B, Son JMV, de la Hoz LC, Garriga M, Garrido-Torres N, Bernardo M, Fernandez-Egea E, Vázquez-Bourgon J. Anthropometry in antipsychotic-naïve first-episode psychosis patients: An exploratory approach to the role of environmental early life events in two independent samples. Schizophr Res 2024; 266:216-226. [PMID: 38428119 DOI: 10.1016/j.schres.2024.02.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 11/14/2023] [Accepted: 02/17/2024] [Indexed: 03/03/2024]
Abstract
BACKGROUND Patients with schizophrenia exhibit a reduced life expectancy mainly due to medical-related pathologies which might have been initiated due to stressful events during fetal development. Indeed, intra-uterus growth patterns predict anthropometric measures in adulthood, describing risk factors for schizophrenia and metabolic disorders. We aim to evaluate anthropometric values in two cohorts of antipsychotic-naïve first-episode episode psychosis (FEP) and correlated them with surrogate markers of the fetal environment such as birth weight (BW) and season of birth. METHODS BW, season of birth, and anthropometric values from 2 cohorts of FEP patients (Barcelona and Santander) were evaluated. In cohort B, 91 patients, and 110 controls while in cohort S, 644 and 235 were included respectively. RESULTS Patients were shorter, slimmer, and with lower BMI compared with controls. In both cohorts, patients, and female patients born in winter displayed the shortest height. Regarding BW, height was significantly associated with the interaction of diagnosis and BW in the whole sample and the male subsample. CONCLUSIONS Our results confirm reduced anthropometric features in FEP at onset while suggesting the influence of winter birth and BW, highlighting the role of early life events in the later outcome of FEP with sex differences.
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Affiliation(s)
- Clemente Garcia-Rizo
- Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Barcelona, Spain; CIBERSAM, ISCIII, Madrid, Spain; Institut d'Investigacions Biomèdiques, August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
| | - Benedicto Crespo-Facorro
- CIBERSAM, ISCIII, Madrid, Spain; Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain.
| | | | - Marcos Gómez-Revuelta
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Institute of Biomedical Research Valdecilla (IDIVAL), Santander, Spain
| | | | - Jacqueline Mayoral-van Son
- CIBERSAM, ISCIII, Madrid, Spain; Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain
| | - Laura Cayón de la Hoz
- Department of Psychiatry, University Hospital Marqués de Valdecilla, Institute of Biomedical Research Valdecilla (IDIVAL), Santander, Spain
| | - Marina Garriga
- CIBERSAM, ISCIII, Madrid, Spain; Institut d'Investigacions Biomèdiques, August Pi I Sunyer (IDIBAPS), Barcelona, Spain; Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Barcelona, Spain
| | - Nathalia Garrido-Torres
- CIBERSAM, ISCIII, Madrid, Spain; Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain
| | - Miguel Bernardo
- Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Departament de Medicina, Institut de Neurociències (UBNeuro), Universitat de Barcelona (UB), Barcelona, Spain; CIBERSAM, ISCIII, Madrid, Spain; Institut d'Investigacions Biomèdiques, August Pi I Sunyer (IDIBAPS), Barcelona, Spain
| | - Emilio Fernandez-Egea
- Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, CB2 0QQ Cambridge, UK; Cambridge shire and Peterborough NHS Foundation Trust, Huntingdon PE29 3RJ, UK
| | - Javier Vázquez-Bourgon
- CIBERSAM, ISCIII, Madrid, Spain; Department of Psychiatry, University Hospital Marqués de Valdecilla, Institute of Biomedical Research Valdecilla (IDIVAL), Santander, Spain; Departamento de Medicina y Psiquiatría, Facultad de Medicina, Universidad de Cantabria, Santander, Spain
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13
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Freire T, Clark X, Pulpitel T, Bell-Anderson K, Ribeiro R, Raubenheimer D, Crean AJ, Simpson SJ, Solon-Biet SM. Maternal macronutrient intake effects on offspring macronutrient targets and metabolism. Obesity (Silver Spring) 2024; 32:743-755. [PMID: 38328970 DOI: 10.1002/oby.23995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 12/04/2023] [Accepted: 12/21/2023] [Indexed: 02/09/2024]
Abstract
OBJECTIVE Exposure in utero to maternal diet can program offspring health and susceptibility to disease. Using C57BL6/JArc mice, we investigated how maternal dietary protein to carbohydrate balance influences male and female offspring appetite and metabolic health. METHODS Dams were placed on either a low-protein (LP) or high-protein (HP) diet. Male and female offspring were placed on a food choice experiment post weaning and were then constrained to either a standard diet or Western diet. Food intake, body weight, and composition were measured, and various metabolic tests were performed at different timepoints. RESULTS Offspring from mothers fed HP diets selected a higher protein intake and had increased body weight in early life relative to offspring from LP diet-fed dams. As predicted by protein leverage theory, higher protein intake targets led to increased food intake when offspring were placed on no-choice diets, resulting in greater body weight and fat mass. The combination of an HP maternal diet and a Western diet further exacerbated this obesity phenotype and led to long-term consequences for body composition and metabolism. CONCLUSIONS This work could help explain the association between elevated protein intake in humans during early life and increased risk of obesity in childhood and later life.
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Affiliation(s)
- Therese Freire
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia
| | - Ximonie Clark
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
| | - Tamara Pulpitel
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
| | - Kim Bell-Anderson
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
| | - Rosilene Ribeiro
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
| | - David Raubenheimer
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
| | - Angela J Crean
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
| | - Stephen J Simpson
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
| | - Samantha M Solon-Biet
- Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia
- School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Camperdown, New South Wales, Australia
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14
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Xhonneux I, Marei WFA, Meulders B, Andries S, Leroy JLMR. The interplay of maternal and offspring obesogenic diets: the impact on offspring metabolism and muscle mitochondria in an outbred mouse model. Front Physiol 2024; 15:1354327. [PMID: 38585221 PMCID: PMC10995298 DOI: 10.3389/fphys.2024.1354327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 03/01/2024] [Indexed: 04/09/2024] Open
Abstract
Consumption of obesogenic (OB) diets increases the prevalence of maternal obesity worldwide, causing major psychological and social burdens in women. Obesity not only impacts the mother's health and fertility but also elevates the risk of obesity and metabolic disorders in the offspring. Family lifestyle is mostly persistent through generations, possibly contributing to the growing prevalence of obesity. We hypothesized that offspring metabolic health is dependent on both maternal and offspring diet and their interaction. We also hypothesized that the sensitivity of the offspring to the diet may be influenced by the match or mismatch between offspring and maternal diets. To test these hypotheses, outbred Swiss mice were fed a control (C, 10% fat, 7% sugar, and n = 14) or OB diet (60% fat, 20% sugar, and n = 15) for 7 weeks and then mated with the same control males. Mice were maintained on the same corresponding diet during pregnancy and lactation, and the offspring were kept with their mothers until weaning. The study focused only on female offspring, which were equally distributed at weaning and fed C or OB diets for 7 weeks, resulting in four treatment groups: C-born offspring fed C or OB diets (C » C and C » OB) and OB-born offspring fed C or OB diets (OB » C and OB » OB). Adult offspring's systemic blood profile (lipid and glucose metabolism) and muscle mitochondrial features were assessed. We confirmed that the offspring's OB diet majorly impacted the offspring's health by impairing the offspring's serum glucose and lipid profiles, which are associated with abnormal muscle mitochondrial ultrastructure. Contrarily, maternal OB diet was associated with increased expression of mitochondrial complex markers and mitochondrial morphology in offspring muscle, but no additive effects of (increased sensitivity to) an offspring OB diet were observed in pups born to obese mothers. In contrast, their metabolic profile appeared to be healthier compared to those born to lean mothers and fed an OB diet. These results are in line with the thrifty phenotype hypothesis, suggesting that OB-born offspring are better adapted to an environment with high energy availability later in life. Thus, using a murine outbred model, we could not confirm that maternal obesogenic diets contribute to female familial obesity in the following generations.
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Affiliation(s)
- Inne Xhonneux
- Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Wilrijk, Belgium
| | - Waleed F. A. Marei
- Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Wilrijk, Belgium
- Department of Theriogenology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Ben Meulders
- Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Wilrijk, Belgium
| | - Silke Andries
- Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Wilrijk, Belgium
| | - Jo L. M. R. Leroy
- Department of Veterinary Sciences, Laboratory of Veterinary Physiology and Biochemistry, Gamete Research Centre, University of Antwerp, Wilrijk, Belgium
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Rocha T, Melson E, Zamora J, Fernandez-Felix BM, Arlt W, Thangaratinam S. Sex-Specific Obesity and Cardiometabolic Disease Risks in Low- and Middle-Income Countries: A Meta-Analysis Involving 3 916 276 Individuals. J Clin Endocrinol Metab 2024; 109:1145-1153. [PMID: 37930879 PMCID: PMC10940259 DOI: 10.1210/clinem/dgad599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Indexed: 11/08/2023]
Abstract
CONTEXT There is limited knowledge about the disparities between the sexes in obesity prevalence and associated cardiovascular complications in low- and middle-income countries (LMICs). OBJECTIVE We undertook a systematic review and meta-analysis to assess sex-specific disparities in the prevalence of obesity and cardiometabolic diseases in LMICs, the burden in women, and variations by region, country's income status, setting, and time. METHODS We searched major databases from inception to March 2023. Two independent reviewers selected the studies, assessed their quality, and extracted data. We used DerSimonian and Laird random-effects models to obtain pooled estimates of odds ratios and 95% CI for the association between sex and obesity and cardiometabolic diseases, and multilevel random-effects logistic regression models to estimate the prevalence of relevant outcomes (PROSPERO CRD42019132609). RESULTS We included 345 studies (3 916 276 individuals). The odds of obesity were 2.72-fold higher in women than men (OR 2.72; 95% CI, 2.54-2.91). The sex-specific disparities varied by region, with the greatest disparities in Sub-Saharan Africa (OR 3.91; 95% CI, 3.49-4.39). Among women in LMICs, 23% (95% CI, 21%-25%) had obesity, 27% (95% CI, 24%-29%) had hypertension, and 7% (95% CI, 6%-9%) had type 2 diabetes. The prevalence of obesity and type 2 diabetes in women varied by region, country's income, and setting, with the highest prevalence in the Middle East and North Africa, upper-middle-income countries and urban settings. The odds of hypertension (OR 2.41; 95% CI, 1.89-3.08) and type 2 diabetes (OR 2.65; 95% CI, 1.76-3.98) were doubled in women with vs without obesity. CONCLUSION There is an urgent need for a women-centred and region-stratified approach to tackle obesity awareness, treatment, and prevention in women in LMICs.
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Affiliation(s)
- Thaís Rocha
- Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- Department of Endocrinology and Diabetes, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK
| | - Eka Melson
- Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- Department of Endocrinology and Diabetes, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, UK
| | - Javier Zamora
- Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid 28034, Spain
- WHO Collaborating Centre for Global Women's Health, Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
| | - Borja Manuel Fernandez-Felix
- Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal de Investigación Sanitaria (IRYCIS), CIBER de Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid 28034, Spain
| | - Wiebke Arlt
- Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham B15 2TQ, UK
- Medical Research Council London Institute of Medical Sciences (MRC LMS), London W12 0HS, UK
| | - Shakila Thangaratinam
- Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- WHO Collaborating Centre for Global Women's Health, Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham B15 2TT, UK
- NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham B15 2TQ, UK
- Birmingham Women's and Children's NHS Foundation Trust, Birmingham B15 2TG, UK
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16
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Lagarde CB, Kavalakatt J, Benz MC, Hawes ML, Arbogast CA, Cullen NM, McConnell EC, Rinderle C, Hebert KL, Khosla M, Belgodere JA, Hoang VT, Collins-Burow BM, Bunnell BA, Burow ME, Alahari SK. Obesity-associated epigenetic alterations and the obesity-breast cancer axis. Oncogene 2024; 43:763-775. [PMID: 38310162 DOI: 10.1038/s41388-024-02954-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 01/18/2024] [Accepted: 01/22/2024] [Indexed: 02/05/2024]
Abstract
Both breast cancer and obesity can regulate epigenetic changes or be regulated by epigenetic changes. Due to the well-established link between obesity and an increased risk of developing breast cancer, understanding how obesity-mediated epigenetic changes affect breast cancer pathogenesis is critical. Researchers have described how obesity and breast cancer modulate the epigenome individually and synergistically. In this review, the epigenetic alterations that occur in obesity, including DNA methylation, histone, and chromatin modification, accelerated epigenetic age, carcinogenesis, metastasis, and tumor microenvironment modulation, are discussed. Delineating the relationship between obesity and epigenetic regulation is vital to furthering our understanding of breast cancer pathogenesis.
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Affiliation(s)
- Courtney B Lagarde
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Joachim Kavalakatt
- Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA
| | - Megan C Benz
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Mackenzie L Hawes
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Carter A Arbogast
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Nicole M Cullen
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Emily C McConnell
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Caroline Rinderle
- Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA
| | - Katherine L Hebert
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Maninder Khosla
- Department of Biochemistry and Molecular Biology, LSU Health Science Center School of Medicine, New Orleans, LA, 70112, USA
| | - Jorge A Belgodere
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
- Department of Biological and Agricultural Engineering, Louisiana State University and Agricultural Center, Baton Rouge, LA, 70803, USA
| | - Van T Hoang
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Bridgette M Collins-Burow
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA
| | - Bruce A Bunnell
- Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, 76107, USA
| | - Matthew E Burow
- Department of Medicine, Section of Hematology and Oncology, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
| | - Suresh K Alahari
- Department of Biochemistry and Molecular Biology, LSU Health Science Center School of Medicine, New Orleans, LA, 70112, USA.
- Stanley S. Scott Cancer Center, LSU Health Science Center School of Medicine, New Orleans, LA, 70112, USA.
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Mucellini AB, Laureano DP, Alves MB, Dalle Molle R, Borges MB, Salvador APDA, Pokhvisneva I, Manfro GG, Silveira PP. The impact of poor fetal growth and chronic hyperpalatable diet exposure in adulthood on hippocampal function and feeding patterns in male rats. Dev Psychobiol 2024; 66:e22459. [PMID: 38372503 DOI: 10.1002/dev.22459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Revised: 12/05/2023] [Accepted: 01/02/2024] [Indexed: 02/20/2024]
Abstract
Poor fetal growth affects eating behavior and the mesocorticolimbic system; however, its influence on the hippocampus has been less explored. Brain insulin sensitivity has been linked to developmental plasticity in response to fetal adversity and to cognitive performance following high-fat diet intake. We investigated whether poor fetal growth and exposure to chronic hyperpalatable food in adulthood could influence the recognition of environmental and food cues, eating behavior patterns, and hippocampal insulin signaling. At 60 days of life, we assigned male offspring from a prenatal animal model of 50% food restriction (FR) to receive either a high-fat and -sugar (HFS) diet or standard chow (CON) diet. Behavioral tests were conducted at 140 days, then tissues were collected. HFS groups showed a diminished hippocampal pAkt/Akt ratio. FR-CON and FR-HFS groups had higher levels of suppressor of cytokine signaling 3, compared to control groups. FR groups showed increased exploration of a novel hyperpalatable food, independent of their diet, and HFS groups exhibited overall lower entropy (less random, more predictable eating behavior) when the environment changed. Poor fetal growth and chronic HFS diet in adulthood altered hippocampal insulin signaling and eating patterns, diminishing the flexibility associated with eating behavior in response to extrinsic changes in food availability in the environment.
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Affiliation(s)
- Amanda Brondani Mucellini
- Graduate Program in Psychiatry and Behavioral Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Daniela Pereira Laureano
- Graduate Program in Neuroscience, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Graduate Program in Child and Adolescent Health, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Márcio Bonesso Alves
- Graduate Program in Biochemistry, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, Quebec, Canada
| | - Roberta Dalle Molle
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, Quebec, Canada
| | - Mariana Balbinot Borges
- Faculty of Biomedicine, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | | | - Irina Pokhvisneva
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, Quebec, Canada
| | - Gisele Gus Manfro
- Graduate Program in Psychiatry and Behavioral Sciences, Faculty of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Graduate Program in Neuroscience, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Patrícia Pelufo Silveira
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Research Centre, McGill University, Montreal, Quebec, Canada
- Department of Psychiatry, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
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18
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Coker SJ, Berry MJ, Vissers MCM, Dyson RM. Maternal Vitamin C Intake during Pregnancy Influences Long-Term Offspring Growth with Timing- and Sex-Specific Effects in Guinea Pigs. Nutrients 2024; 16:369. [PMID: 38337653 PMCID: PMC10857109 DOI: 10.3390/nu16030369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/18/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024] Open
Abstract
Our previous work in guinea pigs revealed that low vitamin C intake during preconception and pregnancy adversely affects fertility, pregnancy outcomes, and foetal and neonatal growth in a sex-dependent manner. To investigate the long-term impact on offspring, we monitored their growth from birth to adolescence (four months), recorded organ weights at childhood equivalence (28 days) and adolescence, and assessed physiological parameters like oral glucose tolerance and basal cortisol concentrations. We also investigated the effects of the timing of maternal vitamin C restriction (early vs. late gestation) on pregnancy outcomes and the health consequences for offspring. Dunkin Hartley guinea pigs were fed an optimal (900 mg/kg feed) or low (100 mg/kg feed) vitamin C diet ad libitum during preconception. Pregnant dams were then randomised into four feeding regimens: consistently optimal, consistently low, low during early pregnancy, or low during late pregnancy. We found that low maternal vitamin C intake during early pregnancy accelerated foetal and neonatal growth in female offspring and altered glucose homeostasis in the offspring of both sexes at an age equivalent to early childhood. Conversely, low maternal vitamin C intake during late pregnancy resulted in foetal growth restriction and reduced weight gain in male offspring throughout their lifespan. We conclude that altered vitamin C during development has long-lasting, sex-specific consequences for offspring and that the timing of vitamin C depletion is also critical, with low levels during early development being associated with the development of a metabolic syndrome-related phenotype, while later deprivation appears to be linked to a growth-faltering phenotype.
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Affiliation(s)
- Sharna J. Coker
- Perinatal and Developmental Physiology Group, Department of Paediatrics and Child Health, University of Otago, Wellington 6242, New Zealand; (M.J.B.); (R.M.D.)
| | - Mary J. Berry
- Perinatal and Developmental Physiology Group, Department of Paediatrics and Child Health, University of Otago, Wellington 6242, New Zealand; (M.J.B.); (R.M.D.)
| | - Margreet C. M. Vissers
- Mātai Hāora-Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago, Christchurch 8140, New Zealand;
| | - Rebecca M. Dyson
- Perinatal and Developmental Physiology Group, Department of Paediatrics and Child Health, University of Otago, Wellington 6242, New Zealand; (M.J.B.); (R.M.D.)
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Miles TK, Allensworth-James ML, Odle AK, Silva Moreira AR, Haney AC, LaGasse AN, Gies AJ, Byrum SD, Riojas AM, MacNicol MC, MacNicol AM, Childs GV. Maternal undernutrition results in transcript changes in male offspring that may promote resistance to high fat diet induced weight gain. Front Endocrinol (Lausanne) 2024; 14:1332959. [PMID: 38720938 PMCID: PMC11077627 DOI: 10.3389/fendo.2023.1332959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 12/14/2023] [Indexed: 05/12/2024] Open
Abstract
Maternal nutrition during embryonic development and lactation influences multiple aspects of offspring health. Using mice, this study investigates the effects of maternal caloric restriction (CR) during mid-gestation and lactation on offspring neonatal development and on adult metabolic function when challenged by a high fat diet (HFD). The CR maternal model produced male and female offspring that were significantly smaller, in terms of weight and length, and females had delayed puberty. Adult offspring born to CR dams had a sexually dimorphic response to the high fat diet. Compared to offspring of maternal control dams, adult female, but not male, CR offspring gained more weight in response to high fat diet at 10 weeks. In adipose tissue of male HFD offspring, maternal undernutrition resulted in blunted expression of genes associated with weight gain and increased expression of genes that protect against weight gain. Regardless of maternal nutrition status, HFD male offspring showed increased expression of genes associated with progression toward nonalcoholic fatty liver disease (NAFLD). Furthermore, we observed significant, sexually dimorphic differences in serum TSH. These data reveal tissue- and sex-specific changes in gene and hormone regulation following mild maternal undernutrition, which may offer protection against diet induced weight gain in adult male offspring.
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Affiliation(s)
- Tiffany K. Miles
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Melody L. Allensworth-James
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Angela K. Odle
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Ana Rita Silva Moreira
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Anessa C. Haney
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Alex N. LaGasse
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Allen J. Gies
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Stephanie D. Byrum
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Angelica M. Riojas
- Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States
| | - Melanie C. MacNicol
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Angus M. MacNicol
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
| | - Gwen V. Childs
- Department of Neurobiology & Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, United States
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Derakhshan M, Kessler NJ, Hellenthal G, Silver MJ. Metastable epialleles in humans. Trends Genet 2024; 40:52-68. [PMID: 38000919 DOI: 10.1016/j.tig.2023.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Revised: 09/20/2023] [Accepted: 09/21/2023] [Indexed: 11/26/2023]
Abstract
First identified in isogenic mice, metastable epialleles (MEs) are loci where the extent of DNA methylation (DNAm) is variable between individuals but correlates across tissues derived from different germ layers within a given individual. This property, termed systemic interindividual variation (SIV), is attributed to stochastic methylation establishment before germ layer differentiation. Evidence suggests that some putative human MEs are sensitive to environmental exposures in early development. In this review we introduce key concepts pertaining to human MEs, describe methods used to identify MEs in humans, and review their genomic features. We also highlight studies linking DNAm at putative human MEs to early environmental exposures and postnatal (including disease) phenotypes.
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Affiliation(s)
- Maria Derakhshan
- London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
| | - Noah J Kessler
- Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK
| | | | - Matt J Silver
- London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK; Medical Research Council (MRC) Unit The Gambia at the London School of Hygiene and Tropical Medicine, Fajara, Banjul, The Gambia.
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21
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Svensson K, Gennings C, Hagenäs L, Wolk A, Håkansson N, Wikström S, Bornehag CG. Maternal nutrition during mid-pregnancy and children's body composition at 7 years of age in the SELMA study. Br J Nutr 2023; 130:1982-1992. [PMID: 37232113 PMCID: PMC10632724 DOI: 10.1017/s0007114523000983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 03/24/2023] [Accepted: 04/12/2023] [Indexed: 05/27/2023]
Abstract
Optimal nutrition during pregnancy is vital for both maternal and child health. Our objective was to explore if prenatal diet is associated with children's height and body fat. Nutrient intake was assessed through a FFQ from 808 pregnant women and summarised to a nutrition index, 'My Nutrition Index' (MNI). The association with children's height and body fat (bioimpedance) was assessed with linear regression models. Secondary analysis was performed with BMI, trunk fat and skinfolds. Overall, higher MNI score was associated with greater height (β = 0·47; (95 % CI 0·00, 0·94), among both sexes. Among boys, higher MNI was associated with 0·15 higher BMI z-scores, 0·12 body fat z-scores, 0·11 trunk fat z-scores, and larger triceps, and triceps + subscapular skinfolds (β = 0·05 and β = 0·06; on the log2 scale) (P-value < 0·05). Among girls, the opposite associations were found with 0·12 lower trunk fat z-scores, and smaller subscapular and suprailiac skinfolds (β = -0·07 and β = -0·10; on the log2 scale) (P-value < 0·05). For skinfold measures, this would represent a ± 1·0 millimetres difference. Unexpectedly, a prenatal diet in line with recommended nutrient intake was associated with higher measures of body fat for boys and opposite to girls at a pre-pubertal stage of development.
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Affiliation(s)
| | - Chris Gennings
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Lars Hagenäs
- Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
| | - Alicja Wolk
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Niclas Håkansson
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Sverre Wikström
- Department of Health Sciences, Karlstad University, Karlstad, Sweden
- Centre for Clinical Research and Education, County Council of Värmland, Värmland County, Sweden
| | - Carl-Gustaf Bornehag
- Department of Health Sciences, Karlstad University, Karlstad, Sweden
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA
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22
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Li S, Nor NM, Kaliappan SR. Long-term effects of child nutritional status on the accumulation of health human capital. SSM Popul Health 2023; 24:101533. [PMID: 37916186 PMCID: PMC10616551 DOI: 10.1016/j.ssmph.2023.101533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 08/09/2023] [Accepted: 10/09/2023] [Indexed: 11/03/2023] Open
Abstract
Research on the impact of childhood nutrition on adult health and human capital has been extensively studied in developed countries, but research in China on this topic is limited. Nowadays, for children's nutritional status, while significant progress has been made in addressing childhood undernutrition in China, regional disparities persist, conversely, the prevalence of childhood overweight continues to rise. For adults' health human capital, the burden of chronic non-communicable diseases among Chinese residents is gradually increasing, over 50% of Chinese residents are overweight or obese, with obesity being one of the risk factors for other chronic diseases. Therefore, this study uses national representative data from 1991 to 2015 China Health and Nutrition Survey (CHNS), matched with individual information from their childhood, to examine the relationship between childhood nutrition and adult health human capital. Based on the two-way fixed effects models and logit models, the study finds that childhood nutrition status measured by height-for-age z score (HAZ) significantly and continuously has been influencing adult health human capital measured by height, BMI, self-rated health (SRH), whether have been sick in last four weeks (SH). BMI-for-age z score (BMIZ) significantly and continuously influence adult health human capital measured by BMI, blood pressure, and perceived stress (PS). Among that, this study places special emphasis on the long-lasting effects of late childhood and adolescence (ages exceeding 6) on the progressive height accumulation and sustained presence of elevated blood pressure. In conclusion, reducing childhood overweight and promoting linear growth and development throughout the whole childhood can reduce the future burden of disease on the nation.
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Affiliation(s)
- Sa Li
- School of Business and Economics, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia
| | - Norashidah Mohamed Nor
- School of Business and Economics, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia
| | - Shivee Ranjanee Kaliappan
- School of Business and Economics, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia
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23
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Tan CM, Tan Z, Zhang X. The intergenerational legacy of the 1959-1961 Great Chinese Famine on children's cognitive development. ECONOMICS AND HUMAN BIOLOGY 2023; 51:101300. [PMID: 37696145 DOI: 10.1016/j.ehb.2023.101300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 08/08/2023] [Accepted: 08/12/2023] [Indexed: 09/13/2023]
Abstract
We investigate the effect of early exposure to malnutrition on the cognitive abilities of the offspring of survivors in the context of a natural experiment; i.e., the Great Chinese Famine (GCF) of 1959-61. We employ a novel dataset - the China Family Panel Studies (CFPS) - to do so. The paper finds that the cognitive abilities of children whose fathers were born in rural areas during the famine years (1959-1961) were impaired by exposure to the GCF and the negative effect was greater for girls than boys, whereas children whose mothers were born in rural areas during the famine years were not affected. The uncovered gender-specific effect is almost entirely attributable to son preference exhibited in families with male famine survivors.
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Affiliation(s)
- Chih Ming Tan
- Department of Economics & Finance, Nistler College of Business and Public Administration, University of North Dakota, Nistler Hall 330P, 3125 University Ave, Stop 8369, Grand Forks, ND 58202-8369, USA.
| | - Zhibo Tan
- International Monetary Fund, 700 19th St, NW, Washington, DC 20431, USA
| | - Xiaobo Zhang
- Guanghua School of Management, Peking University, Beijing 100871, China; International Food Policy Research Institute (IFPRI), 2033 K Street, NW, Washington, DC 20006, USA
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24
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Poveda NE, Adair LS, Martorell R, Patel SA, Ramirez-Zea M, Stein AD. Early life predictors of body composition trajectories from adolescence to mid-adulthood. Am J Hum Biol 2023; 35:e23952. [PMID: 37401888 PMCID: PMC10764641 DOI: 10.1002/ajhb.23952] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 06/14/2023] [Accepted: 06/15/2023] [Indexed: 07/05/2023] Open
Abstract
OBJECTIVES Guatemala has experienced rapid increases in adult obesity. We characterized body composition trajectories from adolescence to mid-adulthood and determined the predictive role of parental characteristics, early life factors, and a nutrition intervention. METHODS One thousand three hundred and sixty-four individuals who participated as children in a nutrition trial (1969-1977) were followed prospectively. Body composition characterized as body mass index (BMI), fat mass index (FMI), and fat-free mass indices (FFMI), was available at four ages between 10 and 55 years. We applied latent class growth analysis to derive sex-specific body composition trajectories. We estimated associations between parental (age, height, schooling) and self-characteristics (birth order, socioeconomic status, schooling, and exposure to a nutrition supplement) with body composition trajectories. RESULTS In women, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and BMI (low: 73.0%; high: 27.0%), and three of FFMI (low: 20.2%; middle: 55.9%; high: 23.9%). In men, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and FFMI (low: 62.4%; high: 37.6%), and three of BMI (low: 43.1%; middle: 46.9%; high: 10.0%). Among women, self's schooling attainment inversely predicted FMI (OR [being in a high latent class]: 0.91, 95% CI: 0.85, 0.97), and maternal schooling positively predicted FFMI (OR: 1.16, 95% CI: 0.97, 1.39). Among men, maternal schooling, paternal age, and self's schooling attainment positively predicted FMI. Maternal schooling positively predicted FFMI, whereas maternal age and paternal schooling were inverse predictors. The nutrition intervention did not predict body composition class membership. CONCLUSIONS Parents' age and schooling, and self's schooling attainment are small but significant predictors of adult body composition trajectories.
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Affiliation(s)
- Natalia E Poveda
- Nutrition and Health Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta GA, USA
| | - Linda S Adair
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Reynaldo Martorell
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta GA, USA
| | - Shivani A Patel
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta GA, USA
| | - Manuel Ramirez-Zea
- INCAP Research Center for the Prevention of Chronic Diseases (CIIPEC), Institute of Nutrition of Central America and Panama (INCAP), Guatemala City, Guatemala
| | - Aryeh D Stein
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta GA, USA
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25
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Andreotti S, Komino ACM, de Fatima Silva F, Ramos APA, Gil NL, Azevedo GA, Sertié RAL, Lima FB, Landgraf RG, Landgraf MA. Intrauterine food restriction impairs the lipogenesis process in the mesenteric adipocytes from low-birth-weight rats into adulthood. Front Endocrinol (Lausanne) 2023; 14:1259854. [PMID: 38027196 PMCID: PMC10651082 DOI: 10.3389/fendo.2023.1259854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 10/09/2023] [Indexed: 12/01/2023] Open
Abstract
Background Intrauterine food restriction (IFR) during pregnancy is associated with low birth weight (LBW) and obesity in adulthood. It is known that white adipose tissue (WAT) plays critical metabolic and endocrine functions; however, this tissue's behavior before weight gain and obesity into adulthood is poorly studied. Thus, we evaluated the repercussions of IFR on the lipogenesis and lipolysis processes in the offspring and described the effects on WAT inflammatory cytokine production and secretion. Methods We induced IFR by providing gestating rats with 50% of the necessary chow daily amount during all gestational periods. After birth, we monitored the offspring for 12 weeks. The capacity of isolated fat cells from mesenteric white adipose tissue (meWAT) to perform lipogenesis (14C-labeled glucose incorporation into lipids) and lipolysis (with or without isoproterenol) was assessed. The expression levels of genes linked to these processes were measured by real-time PCR. In parallel, Multiplex assays were conducted to analyze pro-inflammatory markers, such as IL-1, IL-6, and TNF-α, in the meWAT. Results Twelve-week-old LBW rats presented elevated serum triacylglycerol (TAG) content and attenuated lipogenesis and lipolysis compared to control animals. Inflammatory cytokine levels were increased in the meWAT of LBW rats, evidenced by augmented secretion by adipocytes and upregulated gene and protein expression by the tissue. However, there were no significant alterations in the serum cytokines content from the LBW group. Additionally, liver weight, TAG content in the hepatocytes and serum glucocorticoid levels were increased in the LBW group. Conclusion The results demonstrate that IFR throughout pregnancy yields LBW offspring characterized by inhibited lipogenesis and lipolysis and reduced meWAT lipid storage at 12 weeks. The increased serum TAG content may contribute to the augmented synthesis and secretion of pro-inflammatory markers detected in the LBW group.
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Affiliation(s)
- Sandra Andreotti
- Programa de Pós-Graduação em Medicina Translacional, Universidade Federal de São Paulo, São Paulo, SP, Brazil
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Ayumi Cristina Medeiros Komino
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Flaviane de Fatima Silva
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Ana Paula Almeida Ramos
- Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Noemi Lourenço Gil
- Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Gabriela Araujo Azevedo
- Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Rogerio Antonio Laurato Sertié
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Fabio Bessa Lima
- Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
| | - Richardt Gama Landgraf
- Department of Pharmaceutical Sciences, Universidade Federal de São Paulo, São Paulo, SP, Brazil
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Zhou J, Indik CE, Kuipers TB, Li C, Nivard MG, Ryan CP, Tucker-Drob EM, Taeubert MJ, Wang S, Wang T, Conley D, Heijmans BT, Lumey LH, Belsky DW. Genetic analysis of selection bias in a natural experiment: Investigating in-utero famine effects on elevated body mass index in the Dutch Hunger Winter Families Study. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.10.23.23297381. [PMID: 37961592 PMCID: PMC10635168 DOI: 10.1101/2023.10.23.23297381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2023]
Abstract
Natural-experiment designs that compare survivors of in-utero famine exposure to unaffected controls suggest that in-utero undernutrition predisposes to development of obesity. However, birth rates drop dramatically during famines. Selection bias could arise if factors that contribute to obesity also protect fertility and/or fetal survival under famine conditions. We investigated this hypothesis using genetic analysis of a famine-exposed birth cohort. We genotyped participants in the Dutch Hunger Winter Families Study (DHWFS, N=950; 45% male), of whom 51% were exposed to the 1944-1945 Dutch Famine during gestation and 49% were their unexposed same-sex siblings or "time controls" born before or after the famine in the same hospitals. We computed body-mass index (BMI) polygenic indices (PGIs) in DHWFS participants and compared BMI PGIs between famine-exposed and control groups. Participants with higher polygenic risk had higher BMIs (Pearson r=0.42, p<0.001). However, differences between BMI PGIs of famine-exposed participants and controls were small and not statistically different from zero across specifications (Cohen's d=0.10, p>0.092). Our findings did not indicate selection bias, supporting the validity of the natural-experiment design within DHWFS. In summary, our study outlines a novel approach to explore the presence of selection bias in famine and other natural experiment studies.
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27
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Ji N, Johnson M, Eckel SP, Gauderman WJ, Chavez TA, Berhane K, Faham D, Lurmann F, Pavlovic NR, Grubbs BH, Lerner D, Habre R, Farzan SF, Bastain TM, Breton CV. Prenatal ambient air pollution exposure and child weight trajectories from the 3rd trimester of pregnancy to 2 years of age: a cohort study. BMC Med 2023; 21:341. [PMID: 37674158 PMCID: PMC10483706 DOI: 10.1186/s12916-023-03050-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 08/25/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Prenatal air pollution exposure may increase risk for childhood obesity. However, few studies have evaluated in utero growth measures and infant weight trajectories. This study will evaluate the associations of prenatal exposure to ambient air pollutants with weight trajectories from the 3rd trimester through age 2 years. METHODS We studied 490 pregnant women who were recruited from the Maternal and Development Risks from Environmental and Social Stressors (MADRES) cohort, which comprises a low-income, primarily Hispanic population in Los Angeles, California. Nitrogen dioxide (NO2), particulate matter < 10 µm (PM10), particulate matter < 2.5 µm (PM2.5), and ozone (O3) concentrations during pregnancy were estimated from regulatory air monitoring stations. Fetal weight was estimated from maternal ultrasound records. Infant/child weight measurements were extracted from medical records or measured during follow-up visits. Piecewise spline models were used to assess the effect of air pollutants on weight, overall growth, and growth during each period. RESULTS The mean (SD) prenatal exposure concentrations for NO2, PM2.5, PM10, and O3 were 16.4 (2.9) ppb, 12.0 (1.1) μg/m3, 28.5 (4.7) μg/m3, and 26.2 (2.9) ppb, respectively. Comparing an increase in prenatal average air pollutants from the 10th to the 90th percentile, the growth rate from the 3rd trimester to age 3 months was significantly increased (1.55% [95%CI 1.20%, 1.99%] for PM2.5 and 1.64% [95%CI 1.27%, 2.13%] for NO2), the growth rate from age 6 months to age 2 years was significantly decreased (0.90% [95%CI 0.82%, 1.00%] for NO2), and the attained weight at age 2 years was significantly lower (- 7.50% [95% CI - 13.57%, - 1.02%] for PM10 and - 7.00% [95% CI - 11.86%, - 1.88%] for NO2). CONCLUSIONS Prenatal ambient air pollution was associated with variable changes in growth rate and attained weight from the 3rd trimester to age 2 years. These results suggest continued public health benefits of reducing ambient air pollution levels, particularly in marginalized populations.
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Affiliation(s)
- Nan Ji
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | | | - Sandrah P Eckel
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - William J Gauderman
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Thomas A Chavez
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Kiros Berhane
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, 10032, USA
| | - Dema Faham
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Fred Lurmann
- Sonoma Technology Inc., Petaluma, CA, 94954, USA
| | | | - Brendan H Grubbs
- Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA
| | | | - Rima Habre
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Shohreh F Farzan
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Theresa M Bastain
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA
| | - Carrie V Breton
- Division of Environmental Health, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 1845 N Soto St, MC 9239, Los Angeles, CA, 90039, USA.
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28
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Hull HR, Gajewski BJ, Sullivan DK, Carson SE. Growth and adiposity in newborns study (GAINS): The influence of prenatal DHA supplementation protocol. Contemp Clin Trials 2023; 132:107279. [PMID: 37406769 PMCID: PMC10852997 DOI: 10.1016/j.cct.2023.107279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 06/22/2023] [Accepted: 06/30/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND Obesity and central fat mass (FM) accrual drive disease development and are related to greater morbidity and mortality. Excessive gestational weight gain (GWG) increases fetal fat accretion resulting in greater offspring FM across the lifespan. Studies associate greater maternal docosahexaenoic acid (DHA) levels with lower offspring FM and lower visceral adipose tissue during childhood, however, most U.S. pregnant women do not consume an adequate amount of DHA. We will determine if prenatal DHA supplementation is protective for body composition changes during infancy and toddlerhood in offspring exposed to excessive GWG. METHODS AND DESIGN Infants born to women who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE; NCT02626299) will be invited to participate. Women were randomized to either a high 1000 mg or low 200 mg daily prenatal DHA supplement starting in the first trimester of pregnancy. Offspring body composition and adipose tissue distribution will be measured at 2 weeks, 6 months, 12 months, and 24 months using dual energy x-ray absorptiometry. Maternal GWG will be categorized as excessive or not excessive based on clinical guidelines. DISCUSSION Effective strategies to prevent obesity development are lacking. Exposures during the prenatal period are important in the establishment of the offspring phenotype. However, it is largely unknown which exposures can be successfully targeted to have a meaningful impact. This study will determine if prenatal DHA supplementation modifies the relationship between maternal weight gain and offspring FM and FM distribution at 24 months of age. ETHICS AND DISSEMINATION The University of Kansas Medical Center Institutional Review Board (IRB) approved the study protocol (STUDY00140895). The results of the trial will be disseminated at conferences and in peer reviewed publications. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT03310983.
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Affiliation(s)
- Holly R Hull
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, United States of America.
| | - Byron J Gajewski
- Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, United States of America
| | - Debra K Sullivan
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, United States of America
| | - Susan E Carson
- Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, KS, United States of America
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29
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Jaramillo-Ospina AM, Roman GT, Rodrigues DM, Patel S, Pokhvisneva I, Chakr VG, Levitan RD, Meaney MJ, Silveira PP. Omega-3 polygenic score protects against altered eating behavior in intrauterine growth-restricted children. Pediatr Res 2023; 94:1225-1234. [PMID: 37142650 DOI: 10.1038/s41390-023-02609-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 03/20/2023] [Accepted: 03/30/2023] [Indexed: 05/06/2023]
Abstract
BACKGROUND Alterations in eating behavior are common in infants with intrauterine growth restriction (IUGR); omega-3 polyunsaturated fatty acids (PUFA) could provide protection. We hypothesized that those born IUGR with a genetic background associated with increased production of omega-3-PUFA will have more adaptive eating behaviors during childhood. METHODS IUGR/non-IUGR classified infants from MAVAN and GUSTO cohorts were included at the age of 4 and 5 years, respectively. Their parents reported child's eating behaviors using the child eating behavior questionnaire-CEBQ. Based on the GWAS on serum PUFA (Coltell 2020), three polygenic scores were calculated. RESULTS Significant interactions between IUGR and polygenic score for omega-3-PUFA on emotional overeating (β = -0.15, P = 0.049 GUSTO) and between IUGR and polygenic score for omega-6/omega-3-PUFA on desire to drink (β = 0.35, P = 0.044 MAVAN), pro-intake/anti-intake ratio (β = 0.10, P = 0.042 MAVAN), and emotional overeating (β = 0.16, P = 0.043 GUSTO) were found. Only in IUGR, a higher polygenic score for omega-3-PUFA associated with lower emotional overeating, while a higher polygenic score for omega-6/omega-3-PUFA ratio was associated with a higher desire to drink, emotional overeating, and pro-intake/anti-intake. CONCLUSION Only in IUGR, the genetic background for higher omega-3-PUFA is associated with protection against altered eating behavior, while the genetic score for a higher omega-6/omega-3-PUFA ratio is associated with altered eating behavior. IMPACT A genetic background related to a higher polygenic score for omega-3 PUFA protected infants born IUGR against eating behavior alterations, while a higher polygenic score for omega-6/omega-3 PUFA ratio increased the risk of having eating behavior alterations only in infants born IUGR, irrespective of their adiposity in childhood. Genetic individual differences modify the effect of being born IUGR on eating outcomes, increasing the vulnerability/resilience to eating disorders in IUGR group and likely contributing to their risk for developing metabolic diseases later in life.
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Affiliation(s)
| | - Gabriel T Roman
- Programa de Residência Médica em Medicina Intensiva Pediátrica, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Danitsa M Rodrigues
- Graduate Program in Neurosciences, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Sachin Patel
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
| | - Irina Pokhvisneva
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
| | - Valentina G Chakr
- Departamento de Pediatria, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
| | - Robert D Levitan
- Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Michael J Meaney
- Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Patricia P Silveira
- Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada.
- Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
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Elmighrabi NF, Fleming CAK, Agho KE. Wasting and Underweight in Northern African Children: Findings from Multiple-Indicator Cluster Surveys, 2014-2018. Nutrients 2023; 15:3207. [PMID: 37513624 PMCID: PMC10384034 DOI: 10.3390/nu15143207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/15/2023] [Accepted: 07/16/2023] [Indexed: 07/30/2023] Open
Abstract
Northern Africa faces multiple severe detrimental factors that impact child nutrition. This study aimed to identify the predictors for wasting and underweight in children aged 0-59 months in Northern Africa. We analysed pooled cross-sectional data from multiple-indicator cluster surveys conducted in four countries (Algeria, Egypt, Sudan, and Tunisia) involving 37,816 children aged 0-59 months. A logistic regression analysis was used, considering clustering and sampling weights, to identify factors associated with wasting and underweight among children aged 0-23, 24-59, and 0-59 months. Among children aged 0-59 months, the overall prevalence was 7.2% (95% CI: 6.8-7.5) for wasting and 12.1% (95% CI:11.7-12.5) for underweight. Sudan and Algeria had the highest rates of wasting, while Sudan and Egypt had the highest rates of underweight. Multiple regression analyses indicate that factors associated with wasting and being underweight include child age, country, rural residency, poor wealth index, being male, birth order, maternal education, body mass index, media use, lack of diverse foods, longer duration of breastfeeding, perceived small baby size, and diarrhoea. These findings highlight the importance of implementing targeted health and nutrition initiatives, such as maternal education, family planning, and community engagement. Priority should be given to children from underprivileged areas who lack proper dietary variety.
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Affiliation(s)
- Nagwa Farag Elmighrabi
- School of Health Sciences, Western Sydney University, Campbelltown Campus, Locked Bag 1797, Penrith, NSW 2571, Australia; (C.A.K.F.); (K.E.A.)
- Organization of People of Determination and Sustainable Development, Benghazi, Libya
- Department of Nutrition, Faculty of Public Health, University of Benghazi, Benghazi 1038, Libya
| | - Catharine A. K. Fleming
- School of Health Sciences, Western Sydney University, Campbelltown Campus, Locked Bag 1797, Penrith, NSW 2571, Australia; (C.A.K.F.); (K.E.A.)
- Translational Health Research Institute (THRI), School of Medicine, Western Sydney University, Penrith, NSW 2750, Australia
| | - Kingsley E. Agho
- School of Health Sciences, Western Sydney University, Campbelltown Campus, Locked Bag 1797, Penrith, NSW 2571, Australia; (C.A.K.F.); (K.E.A.)
- Translational Health Research Institute (THRI), School of Medicine, Western Sydney University, Penrith, NSW 2750, Australia
- Faculty of Health Sciences, University of Johannesburg, Johannesburg 2094, South Africa
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Pavela G, Yi N, Mestre L, Xun P, Allison DB. Birth weight moderates the association between obesity and mortality rate. Ann Epidemiol 2023; 82:26-32. [PMID: 37015307 PMCID: PMC10463462 DOI: 10.1016/j.annepidem.2023.03.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 02/14/2023] [Accepted: 03/29/2023] [Indexed: 04/06/2023]
Abstract
PURPOSE The strength of the association between obesity and mortality rate (MR) varies by body mass index (BMI) and sociodemographic groups. We test the hypothesis that the association between obesity and MR varies, in part, due to the moderating effect of parental BMI and birth weight. METHODS Data come from the 1958 National Child Development Study, an ongoing longitudinal dataset initiated in 1958 with baseline measures of birth weight from 18,059 infants born in Great Britain over 1 week. We tested whether the association between BMI and MR was moderated by parental BMI and birth weight using generalized additive proportional hazards models. RESULTS The association between adult BMI and MR was moderated by birth weight and maternal BMI, such that the association between BMI and MR was weaker among individuals with a higher birth weight (P = .0148) and stronger among individuals born to mothers with a higher BMI (P = .032). At any given level of BMI approximately greater than 25, individuals with low birth weight or born to mothers with a higher BMI, had a higher MR. Paternal BMI did not significantly modify the relationship between BMI and MR (P = .5168). CONCLUSIONS Results suggest that the relationship between obesity and MR is modified by birth weight and maternal BMI.
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Affiliation(s)
- Gregory Pavela
- School of Public Health, University of Alabama at Birmingham, Birmingham.
| | - Nengjun Yi
- School of Public Health, University of Alabama at Birmingham, Birmingham
| | - Luis Mestre
- School of Public Health, Indiana University Bloomington, Bloomington
| | | | - David B Allison
- School of Public Health, Indiana University Bloomington, Bloomington
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van Poppel MNM, Damm P, Mathiesen ER, Ringholm L, Zhang C, Desoye G. Is the Biphasic Effect of Diabetes and Obesity on Fetal Growth a Risk Factor for Childhood Obesity? Diabetes Care 2023; 46:1124-1131. [PMID: 37220261 DOI: 10.2337/dc22-2409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Accepted: 03/03/2023] [Indexed: 05/25/2023]
Abstract
In pregnancies of women with obesity or diabetes, neonates are often overgrown. Thus, the pregnancy period in these women offers a window of opportunity to reduce childhood obesity by preventing neonatal overgrowth. However, the focus has been almost exclusively on growth in late pregnancy. This perspective article addresses possible growth deviations earlier in pregnancy and their potential contribution to neonatal overgrowth. This narrative review focuses on six large-scale, longitudinal studies that included ∼14,400 pregnant women with at least three measurements of fetal growth. A biphasic pattern in growth deviation, including growth reduction in early pregnancy followed by overgrowth in late pregnancy, was found in fetuses of women with obesity, gestational diabetes mellitus (GDM), or type 1 diabetes compared with lean women and those with normal glucose tolerance. Fetuses of women with these conditions have reduced abdominal circumference (AC) and head circumference (HC) in early pregnancy (observed between 14 and 16 gestational weeks), while later in pregnancy they present the overgrown phenotype with larger AC and HC (from approximately 30 gestational weeks onwards). Fetuses with early-pregnancy growth reduction who end up overgrown presumably have undergone in utero catch-up growth. Similar to postnatal catch-up growth, this may confer a higher risk of obesity in later life. Potential long-term health consequences of early fetal growth reduction followed by in utero catch-up growth need to be explored.
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Affiliation(s)
| | - Peter Damm
- Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark
- Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Elisabeth R Mathiesen
- Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen, Denmark
| | - Lene Ringholm
- Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark
- Department of Endocrinology and Metabolism, Rigshospitalet, Copenhagen, Denmark
| | - Cuilin Zhang
- Global Center for Asian Women's Health and Asia Center for Reproductive Longevity and Equality, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Department of Obstetrics and Gynecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Gernot Desoye
- Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark
- Department of Obstetrics and Gynaecology, Medical University Graz, Graz, Austria
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Garruti G, Baj J, Cignarelli A, Perrini S, Giorgino F. Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis. Front Endocrinol (Lausanne) 2023; 14:1154561. [PMID: 37274345 PMCID: PMC10236950 DOI: 10.3389/fendo.2023.1154561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 04/07/2023] [Indexed: 06/06/2023] Open
Abstract
Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.
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Affiliation(s)
- Gabriella Garruti
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Jacek Baj
- Department of Anatomy, Medical University of Lublin, Lublin, Poland
| | - Angelo Cignarelli
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Sebastio Perrini
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Francesco Giorgino
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
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Vogt MC, Hobert O. Starvation-induced changes in somatic insulin/IGF-1R signaling drive metabolic programming across generations. SCIENCE ADVANCES 2023; 9:eade1817. [PMID: 37027477 PMCID: PMC10081852 DOI: 10.1126/sciadv.ade1817] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 03/08/2023] [Indexed: 05/30/2023]
Abstract
Exposure to adverse nutritional and metabolic environments during critical periods of development can exert long-lasting effects on health outcomes of an individual and its descendants. Although such metabolic programming has been observed in multiple species and in response to distinct nutritional stressors, conclusive insights into signaling pathways and mechanisms responsible for initiating, mediating, and manifesting changes to metabolism and behavior across generations remain scarce. By using a starvation paradigm in Caenorhabditis elegans, we show that starvation-induced changes in dauer formation-16/forkhead box transcription factor class O (DAF-16/FoxO) activity, the main downstream target of insulin/insulin-like growth factor 1 (IGF-1) receptor signaling, are responsible for metabolic programming phenotypes. Tissue-specific depletion of DAF-16/FoxO during distinct developmental time points demonstrates that DAF-16/FoxO acts in somatic tissues, but not directly in the germline, to both initiate and manifest metabolic programming. In conclusion, our study deciphers multifaceted and critical roles of highly conserved insulin/IGF-1 receptor signaling in determining health outcomes and behavior across generations.
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Chen S, Fan M, Lee BK, Dalman C, Karlsson H, Gardner RM. Rates of maternal weight gain over the course of pregnancy and offspring risk of neurodevelopmental disorders. BMC Med 2023; 21:108. [PMID: 36959571 PMCID: PMC10035205 DOI: 10.1186/s12916-023-02799-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 02/20/2023] [Indexed: 03/25/2023] Open
Abstract
Background Previous studies have suggested that gestational weight gain (GWG) outside an optimal range increases the risks of neurodevelopmental disorders (NDDs) in offspring including autism spectrum disorder (ASD), intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). The sequential development of the fetal brain suggests that its vulnerability may vary depending on the timing of exposure. Therefore, we aimed to investigate the associations of not only gestational age-standardized total GWG (GWG z-scores) but also the rate of GWG (RGWG) in the second and third trimesters with risks of NDDs in offspring. Methods In this population-based cohort study, we used maternal weight data from antenatal care records collected for 57,822 children born to 53,516 mothers between 2007 and 2010 in the Stockholm Youth Cohort. Children were followed from 2 years of age to December 31, 2016. GWG z-scores and RGWG (kg/week) in the second and third trimesters were considered as continuous variables in cox regression models, clustered on maternal identification numbers. Nonlinear relationships were accommodated using restricted cubic splines with 3 knots. RGWG were also categorized according to the 2009 US Institute of Medicine (IOM) guidelines for optimal GWG. According to the IOM guidelines, the optimal rate of GWG for the second and third trimesters for underweight, normal weight, overweight, and obese categories were 0.44–0.58, 0.35–0.50, 0.23–0.33, and 0.17–0.27 kg/week, respectively. Results During a mean follow-up of 5.4 years (until children were on average 7.4 years old), 2205 (3.8%) children were diagnosed with NDDs, of which 1119 (1.9%) received a diagnosis of ASD, 1353 (2.3%) ADHD, and 270 (0.5%) ID. We observed a J-shaped association between total GWG z-score and offspring risk of NDDs, with higher total GWG (GWG z-score = 2) associated with 19% increased risk of any NDD (95% CI = 3–37%) and lower total GWG (GWG z-score = − 2) associated with 12% increased risk of any NDDs (95% CI = 2–23%), compared to the reference (GWG z-score = 0). In the second trimester, lower RGWG (0.25 kg/week) was associated with a 9% increased risk of any NDD diagnosis (95% CI = 4–15%) compared to the median of 0.57 kg/week, with no apparent relationship between higher RGWG and risk of NDDs. In the third trimester, there was no apparent association between lower RGWG and risk of NDDs, though higher RGWG (1 kg/week) was associated with a 28% increased risk of NDD diagnosis (95% CI = 16–40%), compared to the median (0.51 kg/week). When considering categorized RGWG, we found that slow weight gain in the second trimester followed by rapid weight gain in the third trimester most significantly increased the risk of ADHD (HRadjusted = 1.55, 1.13–2.13) and ID (HRadjusted = 2.53, 1.15–5.55) in offspring. The main limitations of our study are the relatively few years for which detailed GWG data were available and the relatively short follow-up for the outcomes, limiting power to detect associations and misclassifying children who receive an NDD diagnosis later in childhood. Conclusions The relationship between maternal weight gain and children’s risk of NDDs varied according to timing in pregnancy, with the greatest risks associated with slow weight gain in the second trimester and rapid weight gain in the third trimester. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-023-02799-6.
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Affiliation(s)
- Shuyun Chen
- grid.4714.60000 0004 1937 0626Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
| | - Mengyu Fan
- grid.4714.60000 0004 1937 0626Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
| | - Brian K. Lee
- grid.4714.60000 0004 1937 0626Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
- grid.166341.70000 0001 2181 3113Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA USA
- A.J. Drexel Autism Institute, Philadelphia, PA USA
| | - Christina Dalman
- grid.4714.60000 0004 1937 0626Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
- grid.425979.40000 0001 2326 2191Centre for Epidemiology and Community Medicine, Stockholm County Council, Stockholm, Sweden
| | - Håkan Karlsson
- grid.4714.60000 0004 1937 0626Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Renee M. Gardner
- grid.4714.60000 0004 1937 0626Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden
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Prenatal exposure to famine and the development of diabetes later in life: an age-period-cohort analysis of the China health and nutrition survey (CHNS) from 1997 to 2015. Eur J Nutr 2023; 62:941-950. [PMID: 36326864 DOI: 10.1007/s00394-022-03049-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 10/25/2022] [Indexed: 11/05/2022]
Abstract
PURPOSE Prenatal exposure to famine has been linked to increased diabetes risk in adulthood. However, one fundamental issue to be addressed is that the reported famine-diabetes relation may be confounded by the age differences between the exposed and non-exposed groups. We aimed to determine the association between prenatal exposure to the Chinese famine of 1959-1962 and risk of diabetes by applying age well-controlled strategies. METHODS Among 20,535 individuals born in 1955-1966 who participated in the China Health and Nutrition Survey from 1997 to 2015, we constructed age-matched exposed vs. non-exposed groups to investigate the role of prenatal exposure to the Chinese famine of 1959-1962 in relation to diabetes. We also built a hierarchical age-period-cohort (HAPC) model to specifically examine the relation of famine to diabetes risk independent of age. RESULTS Compared to the age-balanced men in the non-exposed group, the exposed men born in 1961 had a 154% increased risk of diabetes [odds ratio (OR) 2.54 (95% CI 1.07-6.03), P = 0.04). In the HAPC analysis, the predicted probabilities of diabetes peaked in the 1961-birth cohort of men [3.4% (95% CI 2.4%-5.0%)], as compared to the average probability of diabetes (reference) of 1.8% for men overall. Neither analytical strategy revealed any strong relation between famine exposure and diabetes risk in women. CONCLUSION Among the pre-defined Chinese famine period of 1959-1962, early-life exposure to famine was associated with increased diabetes risk in men but not in women, and these relations were independent of age.
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Maternal Over- and Malnutrition and Increased Risk for Addictive and Eating Disorders in the Offspring. Nutrients 2023; 15:nu15051095. [PMID: 36904093 PMCID: PMC10004806 DOI: 10.3390/nu15051095] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/17/2023] [Accepted: 02/17/2023] [Indexed: 02/24/2023] Open
Abstract
Evidence from human and animal studies has shown that maternal overnutrition and/or obesity are linked with neurobehavioral changes in the offspring. This fetal programming is characterized by adaptive responses to changes in the nutritional state during early life. In the past decade, an association has been made between overconsumption of highly-palatable food by the mother during fetal development and abnormal behaviors resembling addiction in the offspring. Maternal overnutrition can lead to alterations in the offspring's brain reward circuitry leading to hyperresponsiveness of this circuit following exposure to calorie-dense foods later in life. Given the accumulating evidence indicating that the central nervous system plays a pivotal role in regulating food intake, energy balance, and the motivation to seek food, a dysfunction in the reward circuitry may contribute to the addiction-like behaviors observed in the offspring. However, the underlying mechanisms leading to these alterations in the reward circuitry during fetal development and their relevance to the increased risk for the offspring to later develop addictive-like behaviors is still unclear. Here, we review the most relevant scientific reports about the impact of food overconsumption during fetal development and its effect on addictive-like behaviors of the offspring in the context of eating disorders and obesity.
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Dias-Rocha CP, Costa JCB, Oliveira YS, Fassarella LB, Woyames J, Atella GC, Santos GRC, Pereira HMG, Pazos-Moura CC, Almeida MM, Trevenzoli IH. Maternal high-fat diet decreases milk endocannabinoids with sex-specific changes in the cannabinoid and dopamine signaling and food preference in rat offspring. Front Endocrinol (Lausanne) 2023; 14:1087999. [PMID: 36926037 PMCID: PMC10011635 DOI: 10.3389/fendo.2023.1087999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 02/08/2023] [Indexed: 03/08/2023] Open
Abstract
INTRODUCTION Maternal high-fat (HF) diet during gestation and lactation programs obesity in rat offspring associated with sex-dependent and tissue-specific changes of the endocannabinoid system (ECS). The ECS activation induces food intake and preference for fat as well as lipogenesis. We hypothesized that maternal HF diet would increase the lipid endocannabinoid levels in breast milk programming cannabinoid and dopamine signaling and food preference in rat offspring. METHODS Female Wistar rats were assigned into two experimental groups: control group (C), which received a standard diet (10% fat), or HF group, which received a high-fat diet (29% fat) for 8 weeks before mating and during gestation and lactation. Milk samples were collected to measure endocannabinoids and fatty acids by mass spectrometry. Cannabinoid and dopamine signaling were evaluated in the nucleus accumbens (NAc) of male and female weanling offspring. C and HF offspring received C diet after weaning and food preference was assessed in adolescence. RESULTS Maternal HF diet reduced the milk content of anandamide (AEA) (p<0.05) and 2-arachidonoylglycerol (2-AG) (p<0.05). In parallel, maternal HF diet increased adiposity in male (p<0.05) and female offspring (p<0.05) at weaning. Maternal HF diet increased cannabinoid and dopamine signaling in the NAc only in male offspring (p<0.05), which was associated with higher preference for fat in adolescence (p<0.05). CONCLUSION Contrary to our hypothesis, maternal HF diet reduced AEA and 2-AG in breast milk. We speculate that decreased endocannabinoid exposure during lactation may induce sex-dependent adaptive changes of the cannabinoid-dopamine crosstalk signaling in the developing NAc, contributing to alterations in neurodevelopment and programming of preference for fat in adolescent male offspring.
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Affiliation(s)
- Camilla P. Dias-Rocha
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Julia C. B. Costa
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Yamara S. Oliveira
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Larissa B. Fassarella
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Juliana Woyames
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Georgia C. Atella
- Laboratório de Bioquímica de Lipídios e Lipoproteínas, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Gustavo R. C. Santos
- Laboratório de Desenvolvimento Tecnológico, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Henrique M. G. Pereira
- Laboratório de Desenvolvimento Tecnológico, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carmen C. Pazos-Moura
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Mariana M. Almeida
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - Isis H. Trevenzoli
- Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- *Correspondence: Isis H. Trevenzoli,
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Habeos GI, Filippopoulou F, Habeos EE, Kalaitzopoulou E, Skipitari M, Papadea P, Lagoumintzis G, Niarchos A, Georgiou CD, Chartoumpekis DV. Maternal Calorie Restriction Induces a Transcriptional Cytoprotective Response in Embryonic Liver Partially Dependent on Nrf2. Antioxidants (Basel) 2022; 11:2274. [PMID: 36421460 PMCID: PMC9687455 DOI: 10.3390/antiox11112274] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/07/2022] [Accepted: 11/15/2022] [Indexed: 08/27/2023] Open
Abstract
BACKGROUND Calorie restriction is known to enhance Nrf2 signaling and longevity in adult mice, partially by reducing reactive oxygen species, but calorie restriction during pregnancy leads to intrauterine growth retardation. The latter is associated with fetal reprogramming leading to increased incidence of obesity, metabolic syndrome and diabetes in adult life. Transcription factor Nrf2 is a central regulator of the antioxidant response and its crosstalk with metabolic pathways is emerging. We hypothesized that the Nrf2 pathway is induced in embryos during calorie restriction in pregnant mothers. METHODS From gestational day 10 up to day 16, 50% of the necessary mouse diet was provided to Nrf2 heterozygous pregnant females with fathers being of the same genotype. Embryos were harvested at the end of gestational day 16 and fetal liver was used for qRT-PCR and assessment of oxidative stress (OS). RESULTS Intrauterine calorie restriction led to upregulation of mRNA expression of antioxidant genes (Nqo1, Gsta1, Gsta4) and of genes related to integrated stress response (Chac1, Ddit3) in WT embryos. The expression of a key gluconeogenic (G6pase) and two lipogenic genes (Acacb, Fasn) was repressed in calorie-restricted embryos. In Nrf2 knockout embryos, the induction of Nqo1 and Gsta1 genes was abrogated while that of Gsta4 was preserved, indicating an at least partially Nrf2-dependent induction of antioxidant genes after in utero calorie restriction. Measures of OS showed no difference (superoxide radical and malondialdehyde) or a small decrease (thiobarbituric reactive substances) in calorie-restricted WT embryos. CONCLUSIONS Calorie restriction during pregnancy elicits the transcriptional induction of cytoprotective/antioxidant genes in the fetal liver, which is at least partially Nrf2-dependent, with a physiological significance that warrants further investigation.
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Affiliation(s)
- George I. Habeos
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
| | - Fotini Filippopoulou
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
| | - Evagelia E. Habeos
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
| | - Electra Kalaitzopoulou
- Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece
| | - Marianna Skipitari
- Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece
| | - Polyxeni Papadea
- Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece
| | - George Lagoumintzis
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
- Department of Pharmacy, University of Patras, 26504 Patras, Greece
| | - Athanasios Niarchos
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
| | - Christos D. Georgiou
- Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece
| | - Dionysios V. Chartoumpekis
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of Patras, 26504 Patras, Greece
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Song Q, Li N, Sun C, Li Y, King B, Lowe S, Bentley R, Su W, Wang H, Guo X, Liang Q, Liang M, Qu G, Liu H, Ding X, Sun Y. Famine exposure in adolescence is associated with a higher risk of overweight/obesity and abdominal obesity in adulthood: A meta-analysis. Nutr Res 2022; 107:128-138. [PMID: 36215886 DOI: 10.1016/j.nutres.2022.09.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 09/07/2022] [Accepted: 09/12/2022] [Indexed: 12/27/2022]
Abstract
Some studies have shown that famine exposure during adolescence can increase cardiovascular disease and diabetes susceptibility in later life. The association between famine exposure in adolescence and overweight/obesity and abdominal obesity in adulthood has been inconsistent. Based on previous studies, we hypothesized that famine exposure in adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. Eight databases, including PubMed, Embase, Cochrane Library, and Web of Science, were searched from their inception until November 2021. We initially identified 3982 records and finally included 7 articles after screening. The included articles were of moderate to high quality, containing 16 estimates of overweight/obesity and 3 estimates of abdominal obesity. Pooled odds ratios (ORs) with 95% CIs were used to estimate the association between them. The random effects model was adopted as the pooling method. There was a significant association between famine exposure in adolescence and overweight/obesity in adulthood (OR, 1.17; 95% CI, 1.02-1.33). Adolescents exposed to famine had a greater risk of abdominal obesity in adulthood than their unexposed counterparts (OR, 1.35; 95% CI, 1.03-1.76). These results were more pronounced in females than in males. In summary, our meta-analysis indicates that famine exposure during adolescence increases the risk of overweight/obesity and abdominal obesity in adulthood. This suggests that we need to pay timely attention to the nutritional status of adolescents to prevent adverse health consequences of malnutrition. More high-quality studies are needed to confirm these conclusions, given the limitations of this study.
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Affiliation(s)
- Qiuxia Song
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Ning Li
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago, Chicago, IL 60657, USA
| | - Yaru Li
- College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA; Internal Medicine, Swedish Hospital, Chicago, IL 60625, USA
| | - Bethany King
- College of Osteopathic Medicine, Des Moines University, Des Moines, IA, 50312, USA; Internal Medicine, MercyOne Des Moines Medical Center, Des Moines, Iowa 50314, USA
| | - Scott Lowe
- College of Osteopathic Medicine, Kansas City University, Kansas City, MO 64106, USA
| | - Rachel Bentley
- College of Osteopathic Medicine, Kansas City University, Kansas City, MO 64106, USA
| | - Wanying Su
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Hao Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Xianwei Guo
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Qiwei Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Children's Hospital of Anhui Medical University, Hefei 238006, Anhui, China
| | - Mingming Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Guangbo Qu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Haixia Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Xiuxiu Ding
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China
| | - Yehuan Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei 230032, Anhui, China; Chaohu Hospital, Anhui Medical University, Hefei 238006, Anhui, China.
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Kupsco A, Sjödin A, Cowell W, Jones R, Oberfield S, Wang S, Hoepner LA, Gallagher D, Baccarelli AA, Goldsmith J, Rundle AG, Herbstman JB. Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years. Environ Health 2022; 21:82. [PMID: 36076289 PMCID: PMC9454187 DOI: 10.1186/s12940-022-00893-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 08/27/2022] [Indexed: 05/18/2023]
Abstract
BACKGROUND Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/μL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.
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Affiliation(s)
- Allison Kupsco
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th St. Room 1105, New York, NY, 10032, USA.
| | - Andreas Sjödin
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Whitney Cowell
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Richard Jones
- Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Sharon Oberfield
- Division of Pediatric Endocrinology, Diabetes and Metabolism, Department of Pediatrics, New York-Presbyterian Morgan Stanley Children's Hospital, New York, NY, USA
| | - Shuang Wang
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Lori A Hoepner
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th St. Room 1105, New York, NY, 10032, USA
- Department of Environmental and Occupational Health Sciences, School of Public Health, SUNY Downstate Health Sciences University, Brooklyn, NY, USA
| | - Dympna Gallagher
- Nutrition Obesity Research Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Andrea A Baccarelli
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th St. Room 1105, New York, NY, 10032, USA
| | - Jeff Goldsmith
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Andrew G Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Julie B Herbstman
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 722 W 168th St. Room 1105, New York, NY, 10032, USA
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Hunt KJ, Ferguson PL, Neelon B, Commodore S, Bloom MS, Sciscione AC, Grobman WA, Kominiarek MA, Newman RB, Tita AT, Nageotte MP, Palomares K, Skupski DW, Zhang C, Hinkle S, Wapner R, Vena JE. The association between maternal pre-pregnancy BMI, gestational weight gain and child adiposity: A racial-ethnically diverse cohort of children. Pediatr Obes 2022; 17:e12911. [PMID: 35289494 PMCID: PMC9283205 DOI: 10.1111/ijpo.12911] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 02/13/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND The prevalence of obesity in US children has more than tripled in the past 40 years; hence, it is critical to identify potentially modifiable factors that may mitigate the risk. OBJECTIVES To examine the association between maternal pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and child adiposity as measured by BMI, waist circumference and percent body fat in a racial-ethnically diverse cohort. METHODS In a prospective cohort study of healthy women without chronic disease, we examined the association between pre-pregnancy BMI, GWG and child adiposity. Children ages 4-8 years (n = 816) in the Environmental Influences on Child Health Outcomes-NICHD Fetal Growth Studies were assessed. Trained study staff ascertained maternal pre-pregnancy BMI, GWG and child adiposity. RESULTS The odds of child obesity (≥95th BMI percentile) increased independently for each unit increase in maternal pre-pregnancy BMI [OR = 1.12 (95% CI: 1.08, 1.17)] and for each 5-kg increase in GWG [OR = 1.25 (95% CI: 1.07, 1.47)]. The odds of child waist circumference (≥85th percentile) also increased independently for pre-pregnancy BMI [OR = 1.09 (95% CI: 1.05, 1.12)] and GWG [OR = 1.18 (95% CI: 1.04, 1.34)]. CONCLUSIONS Maternal pre-pregnancy BMI and GWG were each independently and positively associated with child obesity and high child waist circumference.
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Affiliation(s)
- Kelly J Hunt
- Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Pamela L Ferguson
- Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Brian Neelon
- Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Sarah Commodore
- Environmental and Occupational Health, Indiana University, Bloomington, Indiana, USA
| | - Michael S Bloom
- Global and Community Health, George Mason University, Fairfax, Virginia, USA
| | - Anthony C Sciscione
- Obstetrics and Gynecology, Christiana Care Health System, Newark, Delaware, USA
| | - William A Grobman
- Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Michelle A Kominiarek
- Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Roger B Newman
- Obstetrics and Gynecology, Medical University of South Carolina, Charleston, South Carolina, USA
| | - Alan T Tita
- Obstetrics and Gynecology and Center for Women's Reproductive Health, University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Michael P Nageotte
- Obstetrics and Gynecology, Miller Children's and Women's Hospital, Long Beach, California, USA
| | - Kristy Palomares
- Obstetrics and Gynecology, Saint Peter's University Hospital, New Brunswick, New Jersey, USA
| | - Daniel W Skupski
- Obstetrics and Gynecology, New York Presbyterian Queens Hospital, Queens, New York, USA
| | - Cuilin Zhang
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Stefanie Hinkle
- Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Ronald Wapner
- Obstetrics and Gynecology, Columbia University Medical Center, New York, New York, USA
| | - John E Vena
- Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
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De Rooij SR, Bleker LS, Painter RC, Ravelli AC, Roseboom TJ. Lessons learned from 25 Years of Research into Long term Consequences of Prenatal Exposure to the Dutch famine 1944-45: The Dutch famine Birth Cohort. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2022; 32:1432-1446. [PMID: 33949901 DOI: 10.1080/09603123.2021.1888894] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 02/08/2021] [Indexed: 06/12/2023]
Abstract
This paper describes the findings of a historical cohort study of men and women born around the time of the Dutch famine 1944-45. It provided the first direct evidence in humans of the lasting consequences of prenatal undernutrition. The effects of undernutrition depended on its timing during gestation, and the organs and tissues undergoing periods of rapid development at that time. Early gestation appeared to be particularly critical, with the effects of undernutrition being most apparent, even without reductions in size at birth. Undernutrition during gestation affected the structure and function of organs and tissues, altered behaviour and increased risks of chronic degenerative diseases. This demonstrates the fundamental importance of maternal nutrition during gestation as the building blocks for future health.
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Affiliation(s)
- Susanne R De Rooij
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Laura S Bleker
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Rebecca C Painter
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Anita C Ravelli
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Department of Medical Informatics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Tessa J Roseboom
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
- Department of Obstetrics and Gynaecology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands
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Keestra SM, Motoc I, Ravelli AC, Roseboom TJ, Finken MJ. Thyroid Function at Age Fifty After Prenatal Famine Exposure in the Dutch Famine Birth Cohort. Front Endocrinol (Lausanne) 2022; 13:836245. [PMID: 35846325 PMCID: PMC9280834 DOI: 10.3389/fendo.2022.836245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Accepted: 05/18/2022] [Indexed: 11/22/2022] Open
Abstract
Background Early-life exposures during gestation may permanently alter thyroid physiology and health in adulthood. We investigated whether exposure to the Dutch Famine (1944-1945) in late, mid, or early gestation influences thyroid function (i.e., incidence of thyroid disease, thyroid autoantibodies, thyroid stimulating hormone (TSH), and free thyroxine (FT4) levels) in adulthood. We specifically assessed whether potential effects of famine differed for men and women. Methods This study includes 910 men and women born as term singletons in the Wilhelmina Gasthuis in Amsterdam, the Netherlands, shortly before, during, or after the Dutch Famine. We evaluated medical histories for previous diagnosis or current treatment for thyroid dysfunction. At age 50 blood samples were drawn from 728 individuals for tests of thyroid function. We studied the prevalence of overt hypo- and hyperthyroidism and thyroid autoimmunity using medical histories, and measurements of TSH, FT4, anti-TPO and anti-TG, comparing participants exposed to famine at different pregnancy trimesters or born before or conceived after the famine. Additionally, we studied associations of TSH and FT4 levels with in utero famine exposure in a subsample of men and women free of thyroid disease that were exposed in late, mid, or early gestation. Results There were no differences in thyroid dysfunction diagnosis or current treatment between participants at age 50 years who been exposed to famine during different periods of gestation and those born before or conceived after. There was no association between famine exposure and overt hypo- or hyperthyroidism or thyroid autoantibody positivity. Women who had been exposed to famine in mid gestation had slightly lower TSH levels than women who had not been exposed to famine prenatally (b=-0.06; 95%; CI=[-0.11,-0.02]; p<0.01). No differences in TSH levels were observed in men, and no differences in FT4 levels were observed in men or women. Conclusions There are no differences in adult thyroid disease at age 50 years according to prenatal famine exposure. However, the lower TSH levels in women exposed to famine in the second trimester suggest that there may be sex-specific effects of famine exposure during a critical period of thyroid development on hypothalamic-pituitary-thyroid axis regulation in adulthood.
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Affiliation(s)
- Sarai M. Keestra
- Department of Epidemiology & Data Science, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
- Department of Reproductive Medicine, Amsterdam University Medical Centre (UMC), Vrije Universiteit Amsterdam, Amsterdam, Netherlands
- Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands
- Department of Paediatric Endocrinology, Amsterdam University Medical Centre (UMC), Vrije Universiteit Amsterdam, Emma Children’s Hospital, Amsterdam, Netherlands
| | - Irina Motoc
- Department of Epidemiology & Data Science, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands
| | - Anita C.J. Ravelli
- Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands
- Department of Medical Informatics, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
- Department of Obstetrics & Gynaecology, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Tessa J. Roseboom
- Department of Epidemiology & Data Science, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
- Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands
- Department of Obstetrics & Gynaecology, Amsterdam University Medical Centre (UMC), University of Amsterdam, Amsterdam, Netherlands
| | - Martijn J.J. Finken
- Amsterdam Reproduction & Development Research Institute, Amsterdam, Netherlands
- Department of Paediatric Endocrinology, Amsterdam University Medical Centre (UMC), Vrije Universiteit Amsterdam, Emma Children’s Hospital, Amsterdam, Netherlands
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Almeida AR, Morita VS, Matos Junior JB, Sgavioli S, Vicentini TI, Boleli IC. Long-Lasting Effects of Incubation Temperature During Fetal Development on Subcutaneous Adipose Tissue of Broilers. Front Physiol 2022; 13:913496. [PMID: 35734000 PMCID: PMC9207451 DOI: 10.3389/fphys.2022.913496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 05/19/2022] [Indexed: 11/30/2022] Open
Abstract
Increasing evidence indicates that fetal programming may cause permanent effects on offspring adipose tissue and body composition. Previous study showed reduction in newly-hatched broiler chick adiposity by manipulating incubation temperature during fetal development. The present study examined whether incubation temperature during fetal development has long-term effects on post-hatching fat deposition in broilers. Broiler breeder eggs (Cobb-500®) were incubated under constant low (36°C, LT), control (37.5°C, CT) or high (39°C, HT) temperature from day 13 onward, giving to eggshell temperature of 37.3 ± 0.08°C, 37.8 ± 0.2°C, and 38.8 ± 0.3°C, respectively. Male chicks were reared under recommended temperatures until 42 days old. LT 21 days old broilers exhibited higher blood cholesterol than CT broilers, and higher triglycerids, VLDL, and LDL, and lower HDL than CT and HT broilers. LT broilers presented higher liver cholesterol than CT broilers and lower ether extract percentage than CT broilers. Adipocyte count was lower in the abdomen than in the thigh. Until day 21 of age, feed intake was higher in LT than in HT broilers. At day 42 of age, blood cholesterol and LDL were higher in HT broilers than in CT and LT broilers. Liver cholesterol was higher in LT than in HT broilers. LT treatment reduced neck and increased thigh adipocyte size compared to CT treatment, while the HT treatment reduced abdomen and neck adipocyte size compared to other two treatments and in the thigh compared to LT treatment. In CT broilers, thigh adipocytes were smaller than abdomen and neck adipocytes. HT treatment increased adipocyte number per area in the neck compared to LT and CT treatment, and LT and HT treatments reduced adipocyte count in the thigh compared to CT treatment. CT broilers presented higher adipocyte count in the thigh than the abdomen and neck, while HT broilers presented higher adipocyte count in the neck than the abdomen and thigh. Cell proliferation was lower in the abdomen than in the thigh. The results show incubation temperature manipulation during fetal development has long-term and distinct effects on regional adiposity, and can be used to modulate broiler fat deposition.
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Affiliation(s)
- Ayla R. Almeida
- Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinary Sciences, Sao Paulo State University—UNESP, Sao Paulo, Brazil
| | - Viviane S. Morita
- Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinary Sciences, Sao Paulo State University—UNESP, Sao Paulo, Brazil
| | | | | | - Tamiris I. Vicentini
- Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinary Sciences, Sao Paulo State University—UNESP, Sao Paulo, Brazil
| | - Isabel C. Boleli
- Department of Animal Morphology and Physiology, Faculty of Agricultural and Veterinary Sciences, Sao Paulo State University—UNESP, Sao Paulo, Brazil
- *Correspondence: Isabel C. Boleli,
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Schroeder M, Badini G, Sferruzzi-Perri AN, Albrecht C. The Consequences of Assisted Reproduction Technologies on the Offspring Health Throughout Life: A Placental Contribution. Front Cell Dev Biol 2022; 10:906240. [PMID: 35747691 PMCID: PMC9210138 DOI: 10.3389/fcell.2022.906240] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 05/05/2022] [Indexed: 11/13/2022] Open
Abstract
The use of assisted reproductive technologies (ART) worldwide has led to the conception and birth of over eight million babies since being implemented in 1978. ART use is currently on the rise, given growing infertility and the increase in conception age among men and women in industrialized countries. Though obstetric and perinatal outcomes have improved over the years, pregnancies achieved by ART still bear increased risks for the mother and the unborn child. Moreover, given that the first generation of ART offspring is now only reaching their forties, the long-term effects of ART are currently unknown. This is important, as there is a wealth of data showing that life-long health can be predetermined by poor conditions during intrauterine development, including irregularities in the structure and functioning of the placenta. In the current review, we aim to summarize the latest available findings examining the effects of ART on the cardiometabolic, cognitive/neurodevelopmental, and behavioral outcomes in the perinatal period, childhood and adolescence/adulthood; and to examine placental intrinsic factors that may contribute to the developmental outcomes of ART offspring. Altogether, the latest knowledge about life outcomes beyond adolescence for those conceived by ART appears to suggest a better long-term outcome than previously predicted. There are also changes in placenta structure and functional capacity with ART. However, more work in this area is critically required, since the potential consequences of ART may still emerge as the offspring gets older. In addition, knowledge of the placenta may help to foresee and mitigate any adverse outcomes in the offspring.
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Affiliation(s)
- Mariana Schroeder
- Faculty of Medicine, Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Gina Badini
- Faculty of Medicine, Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Amanda N. Sferruzzi-Perri
- Centre for Trophoblast Research, Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom
| | - Christiane Albrecht
- Faculty of Medicine, Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
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Development of "Hunger Neurons" and the Unanticipated Relationship Between Energy Metabolism and Mother-Infant Interactions. Biol Psychiatry 2022; 91:907-914. [PMID: 35397878 PMCID: PMC10184517 DOI: 10.1016/j.biopsych.2022.02.962] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 02/18/2022] [Accepted: 02/26/2022] [Indexed: 12/22/2022]
Abstract
Over the course of a lifetime, the perinatal period plays an outsized role in the function of physiological systems. Here, we discuss how neurons that regulate energy metabolism contribute to the infant's relationship with the mother. We focus our discussion on Agrp neurons, which are located in the arcuate nucleus of the hypothalamus. These neurons heavily regulate energy metabolism. Because offspring transition from a period of dependence on the caregiver to independence, we discuss the importance of the caregiver-offspring relationship for the function of Agrp neurons. We present evidence that in the adult, Agrp neurons motivate the animal to eat, while in the neonate, they motivate the offspring to seek the proximity of the caregiver. We specifically highlight the peculiarities in the development of Agrp neurons and how they relate to the regulation of metabolism and behavior over the course of a lifetime. In sum, this review considers the unique insights that ontogenetic studies can offer toward our understanding of complex biological systems, such as the regulation of energy metabolism and mother-infant attachment.
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Sandovici I, Fernandez-Twinn DS, Hufnagel A, Constância M, Ozanne SE. Sex differences in the intergenerational inheritance of metabolic traits. Nat Metab 2022; 4:507-523. [PMID: 35637347 DOI: 10.1038/s42255-022-00570-4] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 04/05/2022] [Indexed: 02/02/2023]
Abstract
Strong evidence suggests that early-life exposures to suboptimal environmental factors, including those in utero, influence our long-term metabolic health. This has been termed developmental programming. Mounting evidence suggests that the growth and metabolism of male and female fetuses differ. Therefore, sexual dimorphism in response to pre-conception or early-life exposures could contribute to known sex differences in susceptibility to poor metabolic health in adulthood. However, until recently, many studies, especially those in animal models, focused on a single sex, or, often in the case of studies performed during intrauterine development, did not report the sex of the animal at all. In this review, we (a) summarize the evidence that male and females respond differently to a suboptimal pre-conceptional or in utero environment, (b) explore the potential biological mechanisms that underlie these differences and (c) review the consequences of these differences for long-term metabolic health, including that of subsequent generations.
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Affiliation(s)
- Ionel Sandovici
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
- Department of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
| | - Denise S Fernandez-Twinn
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Antonia Hufnagel
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK
| | - Miguel Constância
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
- Department of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge, UK.
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
| | - Susan E Ozanne
- Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
- Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
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Arage G, Belachew T, Abate KH. Early life famine exposure and anthropometric profile in adulthood: a systematic review and Meta-analysis. BMC Nutr 2022; 8:36. [PMID: 35459231 PMCID: PMC9028079 DOI: 10.1186/s40795-022-00523-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 03/31/2022] [Indexed: 11/10/2022] Open
Abstract
Background Previous famine studies reported the association between early life famine exposure and adulthood anthropometric profile. However, the findings were variable. Thus, a systematic review and meta-analysis was conducted to clarify the association of famine exposure in early life with the anthropometric profiles in adults. Methods Potentially relevant studies were searched through Scopus, Medline, Google Scholar and Google for gray literature and reference lists of previous studies. The random effects model (REM) and I2 test was used to adapt the pooling method and assess heterogeneity, respectively. Results Prenatal famine exposure was associated with increased risk of body mass index [SMD = 0.10 (95% CI: 0.02, 0.18)], waist circumference [SMD = 0.21 (95% CI: 0.11, 0.31)] in adults. Likewise, famine exposure during prenatal life was associated with decreased adult height [SMD) = − 0.26 (95% CI: − 0.44, − 0.09)]. Moreover, famine exposure during early childhood was associated with increased risk of waist circumference [SMD = 0.09 (95% CI: 0.01, 0.16)] and decreased adult height [SMD = − 0.16 (95% CI: − 0.27, − 0.04)]. Conclusion Our finding indicates that exposure to famine during early life was associated with the anthropometric profile of adults. In terms of public health significance, the results of the study further underscore the importance of improving the nutritional status of mothers and children to prevent adulthood diseases in the long run. Systematic review registration number PROSPERO CRD42020168424 Supplementary Information The online version contains supplementary material available at 10.1186/s40795-022-00523-w.
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Affiliation(s)
- Getachew Arage
- Department of Nutrition and Dietetics, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia. .,Department of Nutrition and Dietetics, Institute of Health, Jimma University, Jimma, Ethiopia.
| | - Tefera Belachew
- Department of Nutrition and Dietetics, Institute of Health, Jimma University, Jimma, Ethiopia
| | - Kalkidan Hassen Abate
- Department of Nutrition and Dietetics, Institute of Health, Jimma University, Jimma, Ethiopia
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Brøns C, Thuesen ACB, Elingaard-Larsen LO, Justesen L, Jensen RT, Henriksen NS, Juel HB, Størling J, Ried-Larsen M, Sparks LM, van Hall G, Danielsen ER, Hansen T, Vaag A. Increased liver fat associates with severe metabolic perturbations in low birth weight men. Eur J Endocrinol 2022; 186:511-521. [PMID: 35212643 DOI: 10.1530/eje-21-1221] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 02/23/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Ectopic liver fat deposition, resulting from impaired subcutaneous adipose tissue expandability, may represent an age-dependent key feature linking low birth weight (LBW) with increased risk of type 2 diabetes (T2D). We examined whether presumably healthy early middle-aged, non-obese LBW subjects exhibit increased liver fat content, whether increased liver fat in LBW is associated with the severity of dysmetabolic traits and finally whether such associations may be confounded by genetic factors. METHODS Using 1H magnetic resonance spectroscopy, we measured hepatic fat content in 26 early middle-aged, non-obese LBW and 22 BMI-matched normal birth weight (NBW) males. Endogenous glucose production was measured by stable isotopes, and a range of plasma adipokine and gut hormone analytes were measured by multiplex ELISA. Genetic risk scores were calculated from genome-wide association study (GWAS) data for birth weight, height, T2D, plasma cholesterol and risk genotypes for non-alcoholic fatty liver disease (NAFLD). RESULTS The LBW subjects had significantly increased hepatic fat content compared with NBW controls (P= 0.014), and 20% of LBW vs no controls had overt NAFLD. LBW subjects with NAFLD displayed widespread metabolic changes compared with NBW and LBW individuals without NAFLD, including hepatic insulin resistance, plasma adipokine and gut hormone perturbations as well as dyslipidemia. As an exception, plasma adiponectin levels were lower in LBW subjects both with and without NAFLD as compared to NBW controls. Genetic risk for selected differential traits did not differ between groups. CONCLUSION Increased liver fat content including overt NAFLD may be on the critical path linking LBW with increased risk of developing T2D in a non-genetic manner.
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Affiliation(s)
- Charlotte Brøns
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
| | - Anne Cathrine Baun Thuesen
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | | | - Rasmus Tanderup Jensen
- Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Helene Bæk Juel
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Joachim Størling
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mathias Ried-Larsen
- Centre for Physical Activity Research (CFAS), Rigshospitalet, Copenhagen, Denmark
| | - Lauren M Sparks
- Translational Research Institute, Advent Health, Orlando, Florida, USA
| | - Gerrit van Hall
- Clinical Metabolomics Core Facility, Rigshospitalet, Copenhagen, Denmark
| | | | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Allan Vaag
- Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
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