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Yau-Qiu ZX, Galmés S, Castillo P, Picó C, Palou A, Rodríguez AM. Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats. Sci Rep 2024; 14:11366. [PMID: 38762543 PMCID: PMC11102553 DOI: 10.1038/s41598-024-62229-2] [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: 02/22/2024] [Accepted: 05/15/2024] [Indexed: 05/20/2024] Open
Abstract
Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.
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Affiliation(s)
- Zhi Xin Yau-Qiu
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Sebastià Galmés
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain.
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain.
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain.
| | - Pedro Castillo
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Catalina Picó
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Andreu Palou
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain
| | - Ana María Rodríguez
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics, Biomarkers and Risk Evaluation-NuBE), University of the Balearic Islands (UIB), Cra. Valldemossa Km 7.5, 07122, Palma, Balearic Islands, Spain
- Health Research Institute of the Balearic Islands (IdISBa), 07120, Palma, Spain
- CIBER of Physiopathology of Obesity and Nutrition (CIBEROBN), Instituto de Salud Carlos III, 28029, Madrid, Spain
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Fernandes DJ, Spring S, Roy AR, Qiu LR, Yee Y, Nieman BJ, Lerch JP, Palmert MR. Exposure to maternal high-fat diet induces extensive changes in the brain of adult offspring. Transl Psychiatry 2021; 11:149. [PMID: 33654064 PMCID: PMC7925669 DOI: 10.1038/s41398-021-01274-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 01/24/2021] [Accepted: 02/05/2021] [Indexed: 12/24/2022] Open
Abstract
Maternal environmental exposures, such as high-fat diets, diabetes and obesity, can induce long-term effects in offspring. These effects include increased risk of neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD), depression and anxiety. The mechanisms underlying these late-life neurologic effects are unknown. In this article, we measured changes in the offspring brain and determined which brain regions are sensitive to maternal metabolic milieu and therefore may mediate NDD risk. We showed that mice exposed to a maternal high-fat diet display extensive brain changes in adulthood despite being switched to a low-fat diet at weaning. Brain regions impacted by early-life diet include the extended amygdalar system, which plays an important role in reward-seeking behaviour. Genes preferentially expressed in these regions have functions related to feeding behaviour, while also being implicated in human NDDs, such as autism. Our data demonstrated that exposure to maternal high-fat diet in early-life leads to brain alterations that persist into adulthood, even after dietary modifications.
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Affiliation(s)
- Darren J Fernandes
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
| | - Shoshana Spring
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
| | - Anna R Roy
- Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada
| | - Lily R Qiu
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK
| | - Yohan Yee
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
- Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada
| | - Brian J Nieman
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Translational Medicine, Hospital for Sick Children, Toronto, ON, Canada
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | - Jason P Lerch
- Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada
- Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK
| | - Mark R Palmert
- Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada.
- Department of Paediatrics and Physiology, University of Toronto, Toronto, ON, Canada.
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Maternal Malnutrition Affects Hepatic Metabolism through Decreased Hepatic Taurine Levels and Changes in HNF4A Methylation. Int J Mol Sci 2020; 21:ijms21239060. [PMID: 33260590 PMCID: PMC7729756 DOI: 10.3390/ijms21239060] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/22/2020] [Accepted: 11/25/2020] [Indexed: 12/16/2022] Open
Abstract
Fetal programming implies that the maternal diet during pregnancy affects the long-term health of offspring. Although maternal diet influences metabolic disorders and non-alcoholic fatty liver disease in offspring, the hepatic mechanisms related to metabolites are still unknown. Here, we investigated the maternal diet-related alterations in metabolites and the biological pathway in male offspring at three months of age. Pregnant rats were exposed to 50% food restriction during the prenatal period or a 45% high-fat diet during the prenatal and postnatal periods. The male offspring exposed to food restriction and high-fat diets had lower birth weights than controls, but had a catch-up growth spurt at three months of age. Hepatic taurine levels decreased in both groups compared to controls. The decreased hepatic taurine levels in offspring affected excessive lipid accumulation through changes in hepatocyte nuclear factor 4 A methylation. Moreover, the alteration of gluconeogenesis in offspring exposed to food restriction was observed to a similar extent as that of offspring exposed to a high fat diet. These results indicate that maternal diet affects the dysregulation in hepatic metabolism through changes in taurine levels and HNF4A methylation, and predisposes the offspring to Type 2 diabetes and non-alcoholic fatty liver disease in later life.
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Yau-Qiu ZX, Picó C, Rodríguez AM, Palou A. Leptin Distribution in Rat Foetal and Extraembryonic Tissues in Late Gestation: A Physiological View of Amniotic Fluid Leptin. Nutrients 2020; 12:E2542. [PMID: 32825787 PMCID: PMC7551401 DOI: 10.3390/nu12092542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/17/2020] [Accepted: 08/19/2020] [Indexed: 12/14/2022] Open
Abstract
Prenatal leptin is key to regulating foetal growth and early metabolic programming. The presence of intact leptin in rat foetal (at late gestation) and neonatal (immediately after birth) stomach content and mucosa has been previously described, suggesting that it may act as a regulatory nutrient for the neonate rats, be internalised by the stomach, and play a physiological role early in life, which requires to be further investigated, including its origin. We aimed to study the ontogeny of the presence of leptin in the foetal stomach and key extraembryonic tissues in rats at late gestation (days 18-21). Leptin concentration was determined by enzyme-linked immunosorbent assay, and placental leptin immunolocalisation was analysed by immunohistochemistry. Leptin showed a sudden appearance in the amniotic fluid (AF) at day 20 of gestation, gastric content (swallowed AF), stomach, and umbilical cord, significantly increasing at day 21. Leptin levels in these fluids and tissues were positively correlated. In the placenta, leptin was detectable at all the studied days, but its localisation changed from widespread throughout the placenta at day 18 to well-defined in the labyrinth zone from day 19 onwards. The results support a possible internalisation of AF leptin by the immature stomach of near-term foetuses and suggest that changes in placental leptin localisation might help to explain the sudden appearance of leptin in AF at gestational day 20, with potential physiological significance regarding short-term feeding control and metabolic programming in the developing offspring.
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Affiliation(s)
- Zhi Xin Yau-Qiu
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics and Obesity), University of the Balearic Islands (UIB), Palma de Mallorca, 07122 Balearic Islands, Spain; (Z.X.Y.-Q.); (C.P.); (A.P.)
- Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, 07010 Balearic Islands, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, 07122 Balearic Islands, Spain
| | - Catalina Picó
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics and Obesity), University of the Balearic Islands (UIB), Palma de Mallorca, 07122 Balearic Islands, Spain; (Z.X.Y.-Q.); (C.P.); (A.P.)
- Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, 07010 Balearic Islands, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, 07122 Balearic Islands, Spain
| | - Ana María Rodríguez
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics and Obesity), University of the Balearic Islands (UIB), Palma de Mallorca, 07122 Balearic Islands, Spain; (Z.X.Y.-Q.); (C.P.); (A.P.)
- Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, 07010 Balearic Islands, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, 07122 Balearic Islands, Spain
| | - Andreu Palou
- Laboratory of Molecular Biology, Nutrition and Biotechnology (Group of Nutrigenomics and Obesity), University of the Balearic Islands (UIB), Palma de Mallorca, 07122 Balearic Islands, Spain; (Z.X.Y.-Q.); (C.P.); (A.P.)
- Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, 07010 Balearic Islands, Spain
- CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, 07122 Balearic Islands, Spain
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Tanaka K, Matsushima M, Izawa T, Furukawa S, Kobayashi Y, Iwashita M. Influence of maternal obesity on fetal growth at different periods of pregnancies with normal glucose tolerance. J Obstet Gynaecol Res 2018; 44:691-696. [DOI: 10.1111/jog.13575] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 11/29/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Kei Tanaka
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Miho Matsushima
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Tomoko Izawa
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Seishi Furukawa
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Yoichi Kobayashi
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Mitsutoshi Iwashita
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
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Tanaka K, Yamada K, Matsushima M, Izawa T, Furukawa S, Kobayashi Y, Iwashita M. Increased maternal insulin resistance promotes placental growth and decreases placental efficiency in pregnancies with obesity and gestational diabetes mellitus. J Obstet Gynaecol Res 2017; 44:74-80. [DOI: 10.1111/jog.13474] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2017] [Accepted: 07/17/2017] [Indexed: 12/28/2022]
Affiliation(s)
- Kei Tanaka
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Kenji Yamada
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Miho Matsushima
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Tomoko Izawa
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Seishi Furukawa
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Yoichi Kobayashi
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
| | - Mitsutoshi Iwashita
- Department of Obstetrics and Gynecology; Kyorin University School of Medicine; Tokyo Japan
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Leon-Garcia SM, Roeder HA, Nelson KK, Liao X, Pizzo DP, Laurent LC, Parast MM, LaCoursiere DY. Maternal obesity and sex-specific differences in placental pathology. Placenta 2015; 38:33-40. [PMID: 26907380 DOI: 10.1016/j.placenta.2015.12.006] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Revised: 11/17/2015] [Accepted: 12/12/2015] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Adverse effects of obesity have been linked to inflammation in various tissues, but studies on placental inflammation and obesity have demonstrated conflicting findings. We sought to investigate the influence of pregravid obesity and fetal sex on placental histopathology while controlling for diabetes and hypertension. METHODS Placental histopathology focusing on inflammatory markers of a cohort of normal weight (BMI = 20-24.9) and obese (BMI ≥ 30) patients was characterized. Demographic, obstetric and neonatal variables were assessed. RESULTS 192 normal and 231 obese women were included. Placental characteristics associated with obesity and fetal sex independent of diabetes and hypertension were placental disc weight >90(th) percentile, decreased placental efficiency, chronic villitis (CV), fetal thrombosis, and normoblastemia. Additionally, female fetuses of obese mothers had higher rates of CV and fetal thrombosis. Increasing BMI increased the risk of normoblastemia and CV. The final grade and extent of CV was significantly associated with obesity and BMI, but not fetal gender. Finally, CV was less common in large-for-gestation placentas. CONCLUSIONS Maternal obesity results in placental overgrowth and fetal hypoxia as manifested by normoblastemia; it is also associated with an increased incidence of CV and fetal thrombosis, both more prevalent in female placentas. We have shown for the first time that the effect of maternal obesity on placental inflammation is independent of diabetes and hypertension, but significantly affected by fetal sex. Our data also point to the intriguing possibility that CV serves to normalize placental size, and potentially fetal growth, in the setting of maternal obesity.
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Affiliation(s)
- Sandra M Leon-Garcia
- Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Hilary A Roeder
- Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Katharine K Nelson
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Xiaoyan Liao
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Donald P Pizzo
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Louise C Laurent
- Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Mana M Parast
- Department of Pathology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - D Yvette LaCoursiere
- Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
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Loardi C, Falchetti M, Prefumo F, Facchetti F, Frusca T. Placental morphology in pregnancies associated with pregravid obesity. J Matern Fetal Neonatal Med 2015; 29:2611-6. [DOI: 10.3109/14767058.2015.1094792] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
Pregestational obesity is a significant risk factor for adverse pregnancy outcomes. Maternal obesity is associated with a specific proinflammatory, endocrine and metabolic phenotype that may lead to higher supply of nutrients to the feto-placental unit and to excessive fetal fat accumulation. In particular, obesity may influence placental fatty acid (FA) transport in several ways, leading to increased diffusion driving force across the placenta, and to altered placental development, size and exchange surface area. Animal models show that maternal obesity is associated with increased expression of specific FA carriers and inflammatory signaling molecules in placental cotyledonary tissue, resulting in enhanced lipid transfer across the placenta, dislipidemia, fat accumulation and possibly altered development in fetuses. Cell culture experiments confirmed that inflammatory molecules, adipokines and FA, all significantly altered in obesity, are important regulators of placental lipid exchange. Expression studies in placentas of obese-diabetic women found a significant increase in FA binding protein-4 expression and in cellular triglyceride content, resulting in increased triglyceride cord blood concentrations. The expression and activity of carriers involved in placental lipid transport are influenced by the endocrine, inflammatory and metabolic milieu of obesity, and further studies are needed to elucidate the strong association between maternal obesity and fetal overgrowth.
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Bolton JL, Bilbo SD. Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. DIALOGUES IN CLINICAL NEUROSCIENCE 2015. [PMID: 25364282 PMCID: PMC4214174 DOI: 10.31887/dcns.2014.16.3/jbolton] [Citation(s) in RCA: 103] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Obesity is now epidemic worldwide. Beyond associated diseases such as diabetes, obesity is linked to neuropsychiatric disorders such as depression. Alarmingly maternal obesity and high-fat diet consumption during gestation/lactation may “program” offspring longterm for increased obesity themselves, along with increased vulnerability to mood disorders. We review the evidence that programming of brain and behavior by perinatal diet is propagated by inflammatory mechanisms, as obesity and high-fat diets are independently associated with exaggerated systemic levels of inflammatory mediators. Due to the recognized dual role of these immune molecules (eg, interleukin [IL]-6, 11-1β) in placental function and brain development, any disruption of their delicate balance with growth factors or neurotransmitters (eg, serotonin) by inflammation early in life can permanently alter the trajectory of fetal brain development. Finally, epigenetic regulation of inflammatory pathways is a likely candidate for persistent changes in metabolic and brain function as a consequence of the perinatal environment.
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Affiliation(s)
- Jessica L Bolton
- Department of Psychology and Neuroscience, Duke Institute for Brain Sciences, Duke University, Durham, North Carolina, USA
| | - Staci D Bilbo
- Department of Psychology and Neuroscience, Duke Institute for Brain Sciences, Duke University, Durham, North Carolina, USA
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11
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Maternal prepregnancy obesity is associated with higher risk of placental pathological lesions. Placenta 2014; 35:563-9. [DOI: 10.1016/j.placenta.2014.05.006] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Revised: 05/09/2014] [Accepted: 05/20/2014] [Indexed: 11/18/2022]
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Portella AK, Silveira PP. Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals. Ann N Y Acad Sci 2014; 1331:15-33. [DOI: 10.1111/nyas.12390] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- André Krumel Portella
- Hospital da Criança Santo Antônio; Santa Casa de Misericórdia de Porto Alegre; Rio Grande do Sul; Brazil
| | - Patrícia Pelufo Silveira
- Departamento de Pediatria, Faculdade de Medicina; Universidade Federal do Rio Grande do Sul; Rio Grande do Sul; Brazil
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Khanal P, Husted SV, Axel AMD, Johnsen L, Pedersen KL, Mortensen MS, Kongsted AH, Nielsen MO. Late gestation over- and undernutrition predispose for visceral adiposity in response to a post-natal obesogenic diet, but with differential impacts on glucose-insulin adaptations during fasting in lambs. Acta Physiol (Oxf) 2014; 210:110-26. [PMID: 23746217 DOI: 10.1111/apha.12129] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2012] [Revised: 02/15/2013] [Accepted: 06/03/2013] [Indexed: 11/26/2022]
Abstract
AIM To investigate if late gestation under- or overnutrition has similar adverse impacts on visceral adiposity, metabolic and endocrine function in sheep, and if subsequent exposure to a high-fat diet in early post-natal life exaggerates the prenatal programming outcomes later in life. METHODS Thirty-six twin-pregnant ewes were fed a NORM (fulfilling 100% of daily requirements for energy and protein), LOW (50% of NORM) or HIGH diet (150% of energy and 110% of protein requirements) during the last 6 weeks of gestation (term = 147 days). Post-natally, the twin lambs were subjected to a high-fat or a moderate diet until 6 months of age (around puberty), where metabolic and endocrine adaptability to fasting was examined, and subgroups of animals were killed. RESULTS Animals exposed to either prenatal under- or overnutrition had reduced subcutaneous fat deposition when fed a high-fat diet, resulting in higher ratios of mesenteric and peri-renal fat relative to subcutaneous fat compared to controls. This was not related to prenatal influences on plasma glucose or insulin. Irrespective of the prenatal diet, high-fat-fed lambs underwent changes resembling the metabolic syndrome with higher plasma glucose, cholesterol, non-esterified fatty acids, triglyceride and lactate combined with abdominal obesity. Peri-renal fat appeared to be a particular target of a high-fat diet post-natally. CONCLUSION Both prenatal under- and overnutrition predisposed for abdominal adiposity, apparently by reducing the expandability of subcutaneous adipose tissue and induced differential physiological adaptations to fasting. This study does not suggest that exposure to gestational overnutrition will provide a protective effect against development of hyperglycaemia later in life.
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Affiliation(s)
- P. Khanal
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - S. V. Husted
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - A. M. D. Axel
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - L. Johnsen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - K. L. Pedersen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - M. S. Mortensen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - A. H. Kongsted
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
| | - M. O. Nielsen
- Department of Veterinary Clinical and Animal Sciences; Faculty of Health and Medical Sciences; University of Copenhagen; Frederiksberg Denmark
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14
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Obesity, diabetes, and the metabolic syndrome: the global scourge. Can J Cardiol 2013; 30:467-72. [PMID: 24530217 DOI: 10.1016/j.cjca.2013.11.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 11/06/2013] [Accepted: 11/06/2013] [Indexed: 01/05/2023] Open
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15
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Bilbo SD. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system. Horm Behav 2013; 63:684-91. [PMID: 23474365 PMCID: PMC3667966 DOI: 10.1016/j.yhbeh.2013.02.017] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2013] [Revised: 02/21/2013] [Accepted: 02/26/2013] [Indexed: 11/26/2022]
Abstract
Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition.
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Affiliation(s)
- Staci D Bilbo
- Department of Psychology and Neuroscience, Duke Institute for Brain Sciences (DIBS), Duke University, Durham, NC 27708, USA.
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Higgins L, Mills TA, Greenwood SL, Cowley EJ, Sibley CP, Jones RL. Maternal obesity and its effect on placental cell turnover. J Matern Fetal Neonatal Med 2013; 26:783-8. [DOI: 10.3109/14767058.2012.760539] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Hayward CE, Higgins L, Cowley EJ, Greenwood SL, Mills TA, Sibley CP, Wareing M. Chorionic plate arterial function is altered in maternal obesity. Placenta 2013; 34:281-7. [PMID: 23360794 PMCID: PMC3605595 DOI: 10.1016/j.placenta.2013.01.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2012] [Revised: 12/23/2012] [Accepted: 01/02/2013] [Indexed: 11/23/2022]
Abstract
Objectives To characterise Chorionic Plate Artery (CPA) function in maternal obesity, and investigate whether leptin exposure reproduces the obese CPA phenotype in normal-BMI women. Study design CPA responses to the thromboxane-A2 mimetic U46619 (pre/post leptin incubation), to the nitric oxide donor sodium nitroprusside (SNP) and the occurrence of tone oscillations (pre/post leptin incubation) were assessed in 46 term placentas from women of normal (18.5–24.9) or obese (>30) Body Mass Index (BMI). Outcome measures Area Under the dose response Curve (AUC), maximum response (Vmax), sensitivity (EC50) to U46619 (pre/post leptin) and SNP; average vessel tone, oscillation amplitude and frequency (pre/post leptin). Results U46619 vasoconstriction was similar between BMI categories (p > 0.05), however vasodilatation to SNP was reduced in obesity (AUC p = 0.02, Vmaxp = 0.04) compared to normal-BMI women. Leptin incubation altered responses to U46619 in both normal-BMI (EC50 at 100 ng/ml leptin; p < 0.05) and obese women (AUC at 50 ng/ml; p < 0.05) but vasomotion was unaffected (p > 0.05). Conclusions Maternal obesity is associated with altered placental vascular function which may adversely affect placental oxygen and nutrient transport, placing the fetus at risk. Leptin incubation altered CPA vascular function but did not reproduce the obese phenotype.
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Affiliation(s)
- C E Hayward
- Maternal and Fetal Health Research Centre, Institute of Human Development, University of Manchester, Manchester Academic Health Science Centre, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, United Kingdom.
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Vambergue A, Fajardy I. Consequences of gestational and pregestational diabetes on placental function and birth weight. World J Diabetes 2011; 2:196-203. [PMID: 22087356 PMCID: PMC3215769 DOI: 10.4239/wjd.v2.i11.196] [Citation(s) in RCA: 136] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2011] [Revised: 10/19/2011] [Accepted: 10/26/2011] [Indexed: 02/05/2023] Open
Abstract
Maternal diabetes constitutes an unfavorable environment for embryonic and fetoplacental development. Despite current treatments, pregnant women with pregestational diabetes are at increased risk for congenital malformations, materno-fetal complications, placental abnormalities and intrauterine malprogramming. The complications during pregnancy concern the mother (gravidic hypertension and/or preeclampsia, cesarean section) and the fetus (macrosomia or intrauterine growth restriction, shoulder dystocia, hypoglycemia and respiratory distress). The fetoplacental impairment and intrauterine programming of diseases in the offspring’s later life induced by gestational diabetes are similar to those induced by type 1 and type 2 diabetes mellitus. Despite the existence of several developmental and morphological differences in the placenta from rodents and women, there are similarities in the alterations induced by maternal diabetes in the placenta from diabetic patients and diabetic experimental models. From both human and rodent diabetic experimental models, it has been suggested that the placenta is a compromised target that largely suffers the impact of maternal diabetes. Depending on the maternal metabolic and proinflammatory derangements, macrosomia is explained by an excessive availability of nutrients and an increase in fetal insulin release, a phenotype related to the programming of glucose intolerance. The degree of fetal damage and placental dysfunction and the availability and utilisation of fetal substrates can lead to the induction of macrosomia or intrauterine growth restriction. In maternal diabetes, both the maternal environment and the genetic background are important in the complex and multifactorial processes that induce damage to the embryo, the placenta, the fetus and the offspring. Nevertheless, further research is needed to better understand the mechanisms that govern the early embryo development, the induction of congenital anomalies and fetal overgrowth in maternal diabetes.
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Affiliation(s)
- Anne Vambergue
- Anne Vambergue, EA 4489 "Perinatal Environment and Fetal Growth", Department of Diabetology, Huriez Hospital, 59800 CHRU Lille, France
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Dubova EA, Pavlov KA, Borovkova EI, Bayramova MA, Makarov IO, Shchegolev AI. Vascular Endothelial Growth Factor and its Receptors in the Placenta of Pregnant Women with Obesity. Bull Exp Biol Med 2011; 151:253-8. [DOI: 10.1007/s10517-011-1302-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Obesity and the placenta: A consideration of nutrient exchange mechanisms in relation to aberrant fetal growth. Placenta 2010; 32:1-7. [PMID: 21030077 DOI: 10.1016/j.placenta.2010.09.019] [Citation(s) in RCA: 79] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Revised: 09/12/2010] [Accepted: 09/30/2010] [Indexed: 01/22/2023]
Abstract
The obesity epidemic, including childhood obesity, is rapidly gaining strength as one of the most significant challenges to the health of the global community in the 21st Century. The proportion of women who are obese at the beginning of pregnancy is also increasing. These women and their babies are at high risk of pregnancy complications, and of programming for metabolic disease in adult life. In particular, maternal obesity is associated with aberrant fetal growth, encompassing both growth restricted and large for gestational age, or macrosomic fetuses. This article considers the potential effect of obesity and adipose tissue on placental nutrient exchange mechanisms in relation to aberrant fetal growth. The review emphasizes the dearth of work on this topic to date despite its importance to current and future healthcare of the population.
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Llewellyn CH, van Jaarsveld CHM, Johnson L, Carnell S, Wardle J. Nature and nurture in infant appetite: analysis of the Gemini twin birth cohort. Am J Clin Nutr 2010; 91:1172-9. [PMID: 20335548 DOI: 10.3945/ajcn.2009.28868] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND A strong genetic influence on appetitive traits has been shown in children and adults, but no studies have examined appetite in early infancy, even though avidity of appetite has been linked with a higher risk of obesity. OBJECTIVE The objective was to investigate the heritability in early infancy of 4 appetitive traits that have been shown to be heritable later in childhood. DESIGN Data are from the Gemini Study, a population-based sample of twins (n = 2402 pairs) born in England and Wales in 2007. To describe their children's eating behavior during the first 3 mo of life while they were still exclusively milk fed, the parents of the twins completed 4 subscales of the Baby Eating Behavior Questionnaire: "enjoyment of food," "food responsiveness," "slowness in eating," and "satiety responsiveness." Heritability was estimated by using quantitative genetic model fitting. RESULTS Heritability was high for slowness in eating (84%; 95% CI: 83%, 86%) and satiety responsiveness (72%; 95% CI: 65%, 80%) and moderate for food responsiveness (59%; 95% CI: 52%, 65%) and enjoyment of food (53%; 95% CI: 43%, 63%). CONCLUSIONS Genetically determined variability in appetitive traits may be one of the pathways through which genes influence the growth rate in infancy. Early identification of infants with avid appetites may make it possible to implement strategies to attenuate the expression of these traits before excessive weight gain occurs.
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Affiliation(s)
- Clare H Llewellyn
- Cancer Research UK Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, United Kingdom
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Harding JE, Derraik JG, Bloomfield FH. Maternal undernutrition and endocrine development. Expert Rev Endocrinol Metab 2010; 5:297-312. [PMID: 30764054 DOI: 10.1586/eem.09.62] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Maternal undernutrition, whether it occurs before conception, throughout gestation or during lactation, may lead to physiological adaptations in the fetus that will affect the health of the offspring in adult life. The timing, severity, duration and nature of the maternal nutritional insult may affect the offspring differently. Other factors determining outcome following maternal undernutrition are fetal number and gender. Importantly, effects of maternal undernutrition may be carried over into subsequent generations. This review examines the endocrine pathways disrupted by maternal undernutrition that affect the long-term postnatal health of the offspring. Maternal and childhood undernutrition are highly prevalent in low- and middle-income countries, and, in developed countries, unintentional undernutrition may arise from maternal dieting. It is, therefore, important that we better understand the mechanisms driving the long-term effects of maternal undernutrition, as well as identifying treatments to ameliorate the associated mortality and morbidity.
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Affiliation(s)
- Jane E Harding
- a Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
| | - José Gb Derraik
- b Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
| | - Frank H Bloomfield
- c Liggins Institute, University of Auckland, Private Bag 92019, Auckland, New Zealand.
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Bilbo SD, Tsang V. Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB J 2010; 24:2104-15. [PMID: 20124437 DOI: 10.1096/fj.09-144014] [Citation(s) in RCA: 387] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
Obesity is well characterized as a systemic inflammatory condition, and is also associated with cognitive disruption, suggesting a link between the two. We assessed whether peripheral inflammation in maternal obesity may be transferred to the offspring brain, in particular, the hippocampus, and thereby result in cognitive dysfunction. Rat dams were fed a high-saturated-fat diet (SFD), a high-trans-fat diet (TFD), or a low-fat diet (LFD) for 4 wk prior to mating, and remained on the diet throughout pregnancy and lactation. SFD/TFD exposure significantly increased body weight in both dams and pups compared to controls. Microglial activation markers were increased in the hippocampus of SFD/TFD pups at birth. At weaning and in adulthood, proinflammatory cytokine expression was strikingly increased in the periphery and hippocampus following a bacterial challenge [lipopolysaccharide (LPS)] in the SFD/TFD groups compared to controls. Microglial activation within the hippocampus was also increased basally in SFD rats, suggesting a chronic priming of the cells. Finally, there were marked changes in anxiety and spatial learning in SFD/TFD groups. These effects were all observed in adulthood, even after the pups were placed on standard chow at weaning, suggesting these outcomes were programmed early in life.
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Affiliation(s)
- Staci D Bilbo
- Duke University, Department of Psychology and Neuroscience, Durham, NC 27708, USA.
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