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Zaina S. The functional significance of vascular DNA hypermethylation in atherosclerosis: a historical perspective. Front Pharmacol 2025; 16:1562674. [PMID: 40303930 PMCID: PMC12037548 DOI: 10.3389/fphar.2025.1562674] [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: 01/17/2025] [Accepted: 04/07/2025] [Indexed: 05/02/2025] Open
Abstract
A decade ago, independent mechanistic and descriptive epigenomics data demonstrated for the first time that vascular DNA hypermethylation is a landmark of and causal factor in human and murine atherosclerosis. Since then, a flurry of converging evidence has assigned a prominent role to vascular DNA hypermethylation across the natural history of cardiovascular disease (CVD), from the exposure to risk factors, to the onset and progression of the atheroma. DNA hypermethylation is induced by and mediates the metabolic outcomes of high-fat diets and CVD risk-enhancing lipids in several models. Early-stage atheroma DNA is hypermethylated compared to normal adjacent tissue, and that trend is amplified as the atheroma progresses. That evidence has resulted in a strong interest for epigenetic drugs in CVD. Crucially, the DNA methylation inhibitor azacytidine has been singled out as a potent guardian of the contractile, anti-atherogenic phenotype of smooth muscle cells (SMC). Those findings are gaining relevance, as the antiatherogenic effects of the anticancer drugs azacytidine and decitabine fit into the recently revived hypothesis that the atheroma is a SMC-driven cancer-like mass. Finally, this 10-year anniversary has been marked by the first report that nanoparticles loaded with a DNA methyltransferase inhibitor drug are anti-inflammatory and inhibit murine atherosclerosis. Exciting work lies ahead to assess whether DNA hypermethylation is a practical and effective target to prevent or cure human atherosclerosis.
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Affiliation(s)
- Silvio Zaina
- Department of Medical Sciences, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Mexico
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Jiao P, Lu H, Hao L, Degen AA, Cheng J, Yin Z, Mao S, Xue Y. Nutrigenetic and Epigenetic Mechanisms of Maternal Nutrition-Induced Glucolipid Metabolism Changes in the Offspring. Nutr Rev 2025; 83:728-748. [PMID: 38781288 DOI: 10.1093/nutrit/nuae048] [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: 05/25/2024] Open
Abstract
Maternal nutrition during pregnancy regulates the offspring's metabolic homeostasis, including insulin sensitivity and the metabolism of glucose and lipids. The fetus undergoes a crucial period of plasticity in the uterus; metabolic changes in the fetus during pregnancy caused by maternal nutrition not only influence fetal growth and development but also have a long-term or even life-long impact for the offspring. Epigenetic modifications, such as DNA methylation, histone modification, and non-coding RNAs, play important roles in intergenerational and transgenerational effects. In this context, this narrative review comprehensively summarizes and analyzes the molecular mechanisms underlying how maternal nutrition, including a high-fat diet, polyunsaturated fatty acid diet, methyl donor nutrient supplementation, feed restriction, and protein restriction during pregnancy, impacts the genes involved in glucolipid metabolism in the liver, adipose tissue, hypothalamus, muscle, and oocytes of the offspring in terms of the epigenetic modifications. This will provide a foundation for the further exploration of nutrigenetic and epigenetic mechanisms for integrative mother-child nutrition and promotion of the offspring's health through the regulation of maternal nutrition during pregnancy. Note: This paper is part of the Nutrition Reviews Special Collection on Precision Nutrition.
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Affiliation(s)
- Peng Jiao
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Huizhen Lu
- Biotechnology Center, Anhui Agricultural University, Hefei, China
| | - Lizhuang Hao
- Key Laboratory of Plateau Grazing Animal Nutrition and Feed Science of Qinghai Province, Qinghai Plateau Yak Research Center, Qinghai Academy of Science and Veterinary Medicine of Qinghai University, Xining, China
| | - A Allan Degen
- Desert Animal Adaptations and Husbandry, Wyler Department of Dryland Agriculture, Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Jianbo Cheng
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Zongjun Yin
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
| | - Shengyong Mao
- College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Yanfeng Xue
- College of Animal Science and Technology, Anhui Agricultural University, Hefei, China
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Song L, Meng M, Ji Y, Peng J, Guan X, Yang Y, Yin XF, Liu T, Tian KP, Bi QH, Wang JP, Li XH, Cai Y, Deng YC. High-fat intake during lactation ameliorates cardiac fatty acid metabolic disorders and dysfunction in mouse offspring undergoing prenatal poly (I:C) stimulation. Acta Pharmacol Sin 2025:10.1038/s41401-025-01497-8. [PMID: 40000881 DOI: 10.1038/s41401-025-01497-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 01/25/2025] [Indexed: 02/27/2025]
Abstract
Prenatal inflammation exposure (PIE) is associated with increased prevalence of cardiovascular diseases (CVDs) in offspring, including heart failure and hypertension. In this study, we investigated the molecular mechanisms underlying the prenatal programming of cardiac function. Pregnant mice were injected with poly (I:C) (20 mg/kg, i.p.) on day 10.5 of gestation. Mothers and pubs were fed with high-fat diet during lactation. Cardiac tissues of the offspring were collected for analysis. We found that prenatal poly (I:C) exposure significantly reduced fatty acid metabolism and impaired the homeostasis of energy metabolism in the heart tissues of offspring at the age of 4 weeks. RNA-sequencing analysis of the heart tissues revealed that prenatal poly (I:C) exposure resulted in decreased expression of the fatty acid oxidation-related enzymes and increased expression of glycolysis-related enzymes, enabling rewiring of energy metabolism. High-fat intake during lactation partially ameliorated cardiac fatty acid metabolism in the heart tissues and prevented cardiac dysfunction in offspring mice exposed to prenatal poly (I:C) at the age of 16 weeks. Collectively, abnormal cardiac fatty acid metabolism accounts for the prenatal poly (I:C) exposure-induced cardiac dysfunction, highlighting the potential of dietary interventions to prevent cardiac dysfunction for PIE offspring.
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Affiliation(s)
- Liang Song
- College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, 400016, China
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
- College of Chinese and Modern Medicine, Chongqing University of Chinese Medicine, Chongqing, 402760, China
| | - Meng Meng
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
- School of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China
| | - Yan Ji
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
| | - Jian Peng
- Biobank Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
| | - Xiao Guan
- Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China
| | - Yao Yang
- Department of Pharmacy, The General Hospital of Western Theater Command of PLA, Chengdu, 610083, China
| | - Xiao-Feng Yin
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
| | - Tao Liu
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
| | - Kun-Peng Tian
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
| | - Qing-Hua Bi
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China
| | - Jun-Ping Wang
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China
| | - Xiao-Hui Li
- Institute of Materia Medica, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China.
| | - Yue Cai
- Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710000, China.
| | - You-Cai Deng
- Department of Clinical Hematology, College of Pharmacy and Laboratory Medicine Science, Army Medical University, Chongqing, 400038, China.
- State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Army Medical University, Chongqing, 400038, China.
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Cheng H, Wu J, Peng H, Li J, Liu Z, Wang X, Zhang K, Xie L. Epigenetic Modulation with 5-Aza-CdR Prevents Metabolic-Associated Fatty Liver Disease Promoted by Maternal Overnutrition. Nutrients 2024; 17:106. [PMID: 39796540 PMCID: PMC11722594 DOI: 10.3390/nu17010106] [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: 10/28/2024] [Revised: 12/03/2024] [Accepted: 12/12/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND/OBJECTIVES This study builds on previous findings from mouse models, which showed that maternal overnutrition induced by a high-fat diet (HFD) promotes metabolic-associated fatty liver disease (MAFLD) in offspring, linked to global DNA hypermethylation. We explored whether epigenetic modulation with 5-Aza-CdR, a DNA methylation inhibitor, could prevent MAFLD in offspring exposed to maternal overnutrition. METHODS The offspring mice from dams of maternal overnutrition were fed either a chow diet or a high-fat diet (HFD) for 10 weeks. These mice were randomly divided into two groups: HFD, and AZA + HFD. Mice assigned to the AZA group were given 5-Aza-CdR during the last three weeks. RESULTS Our findings show that 5-Aza-CdR treatment in HFD-fed offspring effectively countered weight gain, improved glucose regulation, and minimized hepatic fat buildup along with serum lipid imbalances. Additionally, it boosted AMPK signaling and raised PPAR-α expression, pointing to enhanced fatty acid oxidation. We also detected an increase in JNK signaling, affecting the gene expression associated with cell death and proliferation. Notably, treated mice displayed more hepatic inflammation than the HFD group alone, suggesting a complex, dual impact on MAFLD management. Significant apoptotic and inflammatory gene changes were identified, along with corresponding differentially methylated regions triggered by 5-Aza-CdR, marking potential therapeutic targets. CONCLUSIONS 5-Aza-CdR was shown to mitigate MAFLD features in offspring of maternal overnutrition by reversing DNA hypermethylation and improving metabolic pathways, though its dual impact on inflammation highlights the need for further research to optimize its therapeutic potential.
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Affiliation(s)
- Henghui Cheng
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
| | - Jie Wu
- Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; (J.W.); (J.L.)
| | - Hui Peng
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
| | - Jiangyuan Li
- Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; (J.W.); (J.L.)
- Department of Statistics, Texas A&M University, College Station, TX 77843, USA
| | - Zhimin Liu
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
| | - Xian Wang
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
| | - Ke Zhang
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
- Center for Epigenetics & Disease Prevention, Institute of Biosciences & Technology, College of Medicine, Texas A&M University, Houston, TX 77030, USA; (J.W.); (J.L.)
| | - Linglin Xie
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA; (H.C.); (H.P.); (Z.L.); (X.W.)
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Flores-Sierra JDJ, Muciño-Arellano MDR, Romo-Morales GDC, Sánchez-Palafox JE, Correa-Navarro VA, Colín-Castelán D, Pérez-Vázquez V, Rangel-Salazar R, Rivera-Bustamante R, de la Rocha C, Rodríguez-Ríos D, Trejo-Saavedra DL, Molina-Torres J, Ramírez-Chávez E, García-Rojas NS, Winkler R, Lund G, Zaina S. The DNA methyltransferase inhibitor decitabine blunts the response to a high-animal fat and protein diet in mice. J Lipid Res 2024; 65:100586. [PMID: 38942113 PMCID: PMC11325794 DOI: 10.1016/j.jlr.2024.100586] [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: 05/28/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 06/30/2024] Open
Abstract
Increasing evidence hints that DNA hypermethylation may mediate the pathogenic response to cardiovascular risk factors. Here, we tested a corollary of that hypothesis, that is, that the DNA methyltransferase inhibitor decitabine (Dec) ameliorates the metabolic profile of mice fed a moderately high-animal fat and protein diet (HAFPD), a proxy of cardiovascular risk-associated Western-type diet. HAFPD-fed mice were exposed to Dec or vehicle for eight weeks (8W set, 4-32/group). To assess any memory of past exposure to Dec, we surveyed a second mice set treated as 8W but HAFPD-fed for further eight weeks without any Dec (16W set, 4-20/group). In 8W, Dec markedly reduced HAFPD-induced body weight gain in females, but marginally in males. Characterization of females revealed that Dec augmented skeletal muscle lipid content, while decreasing liver fat content and increasing plasma nonesterified fatty acids, adipose insulin resistance, and-although marginally-whole blood acylcarnitines, compared to HAFPD alone. Skeletal muscle mitochondrial DNA copy number was higher in 8W mice exposed to HAFPD and Dec, or in 16W mice fed HAFPD only, relative to 8W mice fed HAFPD only, but Dec induced a transcriptional profile indicative of ameliorated mitochondrial function. Memory of past Dec exposure was tissue-specific and sensitive to both duration of exposure to HAFPD and age. In conclusion, Dec redirected HAFPD-induced lipid accumulation toward the skeletal muscle, likely due to augmented mitochondrial functionality and increased lipid demand. As caveat, Dec induced adipose insulin resistance. Our findings may help identifying strategies for prevention and treatment of lipid dysmetabolism.
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Affiliation(s)
- José de Jesús Flores-Sierra
- Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico; Tecnológico Nacional de México/ITS de Purísima del Rincón, Purísima del Rincón, Guanajuato, Mexico
| | | | | | | | | | - Dannia Colín-Castelán
- Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico
| | - Victoriano Pérez-Vázquez
- Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico
| | - Rubén Rangel-Salazar
- Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico
| | | | - Carmen de la Rocha
- Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico
| | | | | | - Jorge Molina-Torres
- Department of Biotechnology and Biochemistry, CINVESTAV Irapuato Unit, Irapuato, Mexico
| | | | | | | | - Gertrud Lund
- Department of Genetic Engineering, CINVESTAV Irapuato Unit, Irapuato, Mexico.
| | - Silvio Zaina
- Division of Health Sciences, Department of Medical Sciences, Leon Campus, University of Guanajuato, Leon, Mexico.
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Rostami A, White K, Rostami K. Pro and anti-inflammatory diets as strong epigenetic factors in inflammatory bowel disease. World J Gastroenterol 2024; 30:3284-3289. [PMID: 39086746 PMCID: PMC11287421 DOI: 10.3748/wjg.v30.i27.3284] [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: 04/07/2024] [Revised: 06/16/2024] [Accepted: 06/28/2024] [Indexed: 07/11/2024] Open
Abstract
Inflammatory bowel disease (IBD) is the consequence of a complex interplay between environmental factors, like dietary habits, that alter intestinal microbiota in response to luminal antigens in genetically susceptible individuals. Epigenetics represents an auspicious area for the discovery of how environmental factors influence the pathogenesis of inflammation, prognosis, and response to therapy. Consequently, it relates to gene expression control in response to environmental influences. The increasing number of patients with IBD globally is indicative of the negative effects of a food supply rich in trans and saturated fats, refined sugars, starches and additives, as well as other environmental factors like sedentarism and excess bodyweight, influencing the promotion of gene expression and increasing DNA hypomethylation in IBD. As many genetic variants are now associated with Crohn's disease (CD), new therapeutic strategies targeting modifiable environmental triggers, such as the implementation of an anti-inflammatory diet that involves the removal of potential food antigens, are of growing interest in the current literature. Diet, as a strong epigenetic factor in the pathogenesis of inflammatory disorders like IBD, provides novel insights into the pathophysiology of intestinal and extraintestinal inflammatory disorders.
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Affiliation(s)
- Adele Rostami
- Digestive Health Clinic, Palmerston North 4410, New Zealand
| | - Kristen White
- Digestive Health Clinic & Kōtare Wellness Ltd, Palmerston North 4410, New Zealand
| | - Kamran Rostami
- Department of Gastroenterology, Palmerston North Hospital, Palmerston North 4442, New Zealand
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Gündüz B, Okimoto DK. Methyl donor supplementation alters serum leptin levels and increases appetite but not body weight in cross-fostered male Syrian hamster offspring (Mesocricetus auratus). J Anim Physiol Anim Nutr (Berl) 2022; 106:1130-1138. [PMID: 34865266 DOI: 10.1111/jpn.13665] [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: 05/13/2021] [Accepted: 11/11/2021] [Indexed: 11/29/2022]
Abstract
A pregnant hamster's exposure to changes in environmental factors, such as light, temperature and nutrition, may influence behavioural and physiological changes in offspring. In this study, dietary methyl donor supplementation was employed to examine the role of maternal diet on appetite, body weight, serum leptin levels and locomotor activity in male Syrian hamster offspring. Dams were fed a standard control (SC) or methyl donor-supplemented (MDSD) diet through pregnancy and lactation. At birth, offspring were cross-fostered to dams fed an SC or MDSD diet (SC-MDSD and MDSD-SC) or remained with their birth mothers (SC-SC and MDSD-MDSD). At weaning, offspring were fed a SC or MDSD diet until 60 days of age. Food intake, serum leptin levels and locomotor activity were measured from 30-60 days of age. Offspring fed a MDSD diet post-weaning (MDSD-MDSD and SC-MDSD) consumed more than double the amount of food daily compared with offspring fed a SC diet post-weaning (SC-SC, MDSD-SC). Interestingly, there were no observed differences in body weight among all four groups. Serum leptin levels at 60 days of age were depressed in offspring fed a MDSD diet post-weaning (MDSD-MDSD and SC-MDSD). There were no observed differences in wheel running activity between the SC-SC and MDSC-SC groups. Wheel running activity was at least twice the amount in offspring fed a MDSD diet post-weaning (SC-MDSD and MDSD-MDSD). Taken together, these results indicate that the timing of methyl donor supplementation appears to be an important factor during the development of offspring.
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Affiliation(s)
- Bülent Gündüz
- Faculty of Arts and Sciences, Department of Biology, Canakkale Onsekiz Mart University, Canakkale, Turkey
| | - Darren K Okimoto
- University of Hawaii Sea Grant College Program, University of Hawaii at Manoa, Honolulu, Hawaii, USA
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Comparative Transcriptomics and Methylomics Reveal Adaptive Responses of Digestive and Metabolic Genes to Dietary Shift in Giant and Red Pandas. Genes (Basel) 2022; 13:genes13081446. [PMID: 36011357 PMCID: PMC9407821 DOI: 10.3390/genes13081446] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/01/2022] [Accepted: 08/12/2022] [Indexed: 11/17/2022] Open
Abstract
Both the giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens) belong to the order Carnivora, but have changed their dietary habits to eating bamboo exclusively. The convergent evolution characteristics of their morphology, genome and gut flora have been found in the two pandas. However, the research on the convergent adaptation of their digestion and metabolism to the bamboo diet, mediated by the dietary shift of the two pandas at the gene-expression and epigenetic regulation levels, is still lacking. We therefore used RNA sequencing among five species (two pandas and three non-herbivore mammals) and bisulfite sequencing among three species (two pandas and a carnivore ferret) to sequence key digestion and metabolism tissues (stomach and small intestine). Our results provide evidence that the convergent differentially expressed genes (related to carbohydrate utilization, bile secretion, Lys and Arg metabolism, vitamin B12 utilization and cyanide detoxification) of the two pandas are adaptive responses to the bamboo diet containing low lipids, low Lys and Arg, low vitamin B12 and high cyanide. We also profiled the genome-wide methylome maps of giant panda, red panda and ferret, and the results indicated that the promoter methylation of the two pandas may regulate digestive and metabolic genes to adapt to sudden environmental changes, and then, transmit genetic information to future generations to evolve into bamboo eaters. Taken together, our study provides new insights into the molecular mechanisms of the dietary shift and the adaptation to a strict bamboo diet in both pandas using comparative transcriptomics and methylomics.
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Wilson NRC, Veatch OJ, Johnson SM. On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics. Biomedicines 2022; 10:668. [PMID: 35327470 PMCID: PMC8945691 DOI: 10.3390/biomedicines10030668] [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: 12/16/2021] [Revised: 02/17/2022] [Accepted: 03/01/2022] [Indexed: 12/21/2022] Open
Abstract
This review offers an overview of the relationship between diabetes, obstructive sleep apnea (OSA), obesity, and heart disease. It then addresses evidence that the traditional understanding of this relationship is incomplete or misleading. In the process, there is a brief discussion of the evolutionary rationale for the development and retention of OSA in light of blood sugar dysregulation, as an adaptive mechanism in response to environmental stressors, followed by a brief overview of the general concepts of epigenetics. Finally, this paper presents the results of a literature search on the epigenetic marks and changes in gene expression found in OSA and diabetes. (While some of these marks will also correlate with obesity and heart disease, that is beyond the scope of this project). We conclude with an exploration of alternative explanations for the etiology of these interlinking diseases.
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Affiliation(s)
- N. R. C. Wilson
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA;
| | - Olivia J. Veatch
- Department of Psychiatry & Behavioral Sciences, University of Kansas Medical Center, Kansas City, KS 66160, USA;
| | - Steven M. Johnson
- Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA;
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Li Y, Pollock CA, Saad S. Aberrant DNA Methylation Mediates the Transgenerational Risk of Metabolic and Chronic Disease Due to Maternal Obesity and Overnutrition. Genes (Basel) 2021; 12:genes12111653. [PMID: 34828259 PMCID: PMC8624316 DOI: 10.3390/genes12111653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 10/02/2021] [Accepted: 10/17/2021] [Indexed: 12/13/2022] Open
Abstract
Maternal obesity is a rapidly evolving universal epidemic leading to acute and long-term medical and obstetric health issues, including increased maternal risks of gestational diabetes, hypertension and pre-eclampsia, and the future risks for offspring's predisposition to metabolic diseases. Epigenetic modification, in particular DNA methylation, represents a mechanism whereby environmental effects impact on the phenotypic expression of human disease. Maternal obesity or overnutrition contributes to the alterations in DNA methylation during early life which, through fetal programming, can predispose the offspring to many metabolic and chronic diseases, such as non-alcoholic fatty liver disease, obesity, diabetes, and chronic kidney disease. This review aims to summarize findings from human and animal studies, which support the role of maternal obesity in fetal programing and the potential benefit of altering DNA methylation to limit maternal obesity related disease in the offspring.
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Affiliation(s)
- Yan Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China;
| | - Carol A. Pollock
- Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia;
| | - Sonia Saad
- Kolling Institute of Medical Research, University of Sydney, Sydney, NSW 2065, Australia;
- Correspondence:
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11
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Acevedo N, Alashkar Alhamwe B, Caraballo L, Ding M, Ferrante A, Garn H, Garssen J, Hii CS, Irvine J, Llinás-Caballero K, López JF, Miethe S, Perveen K, Pogge von Strandmann E, Sokolowska M, Potaczek DP, van Esch BCAM. Perinatal and Early-Life Nutrition, Epigenetics, and Allergy. Nutrients 2021; 13:724. [PMID: 33668787 PMCID: PMC7996340 DOI: 10.3390/nu13030724] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/08/2021] [Accepted: 02/12/2021] [Indexed: 02/08/2023] Open
Abstract
Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.
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Affiliation(s)
- Nathalie Acevedo
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Bilal Alashkar Alhamwe
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35043 Marburg, Germany; (B.A.A.); (E.P.v.S.)
- College of Pharmacy, International University for Science and Technology (IUST), Daraa 15, Syria
| | - Luis Caraballo
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Mei Ding
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland; (M.D.); (M.S.)
- Christine Kühne-Center for Allergy Research and Education, 7265 Davos, Switzerland
- Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
| | - Antonio Ferrante
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
- School of Biological Sciences, University of Adelaide, Adelaide, SA 5005, Australia
| | - Holger Garn
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands;
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
| | - Charles S. Hii
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - James Irvine
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Kevin Llinás-Caballero
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Juan Felipe López
- Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia; (N.A.); (L.C.); (K.L.-C.); (J.F.L.)
| | - Sarah Miethe
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Khalida Perveen
- Department of Immunopathology, SA Pathology at the Women’s and Children’s Hospital, North Adelaide, SA 5006, Australia; (A.F.); (C.S.H.); (J.I.); (K.P.)
- Adelaide School of Medicine and the Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia
| | - Elke Pogge von Strandmann
- Institute of Tumor Immunology, Clinic for Hematology, Oncology and Immunology, Center for Tumor Biology and Immunology, Philipps University Marburg, 35043 Marburg, Germany; (B.A.A.); (E.P.v.S.)
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, 7265 Davos, Switzerland; (M.D.); (M.S.)
- Christine Kühne-Center for Allergy Research and Education, 7265 Davos, Switzerland
| | - Daniel P. Potaczek
- Translational Inflammation Research Division & Core Facility for Single Cell Multiomics, Medical Faculty, Philipps University Marburg, Member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center, 35043 Marburg, Germany; (H.G.); (S.M.)
| | - Betty C. A. M. van Esch
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands;
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands
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12
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Ramos LF, Silva CM, Pansa CC, Moraes KCM. Non-alcoholic fatty liver disease: molecular and cellular interplays of the lipid metabolism in a steatotic liver. Expert Rev Gastroenterol Hepatol 2021; 15:25-40. [PMID: 32892668 DOI: 10.1080/17474124.2020.1820321] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) affects ~25% of world population and cases have increased in recent decades. These anomalies have several etiologies; however, obesity and metabolic dysfunctions are the most relevant causes. Despite being considered a public health problem, no effective therapeutic approach to treat NAFLD is available. For that, a deep understanding of metabolic routes that support hepatic diseases is needed. AREAS COVERED This review covers aspects of the onset of NAFLD. Thereby, biochemistry routes as well as cellular and metabolic effects of the gut microbiota in body's homeostasis and epigenetics are contextualized. EXPERT OPINION Recently, the development of biological sciences has generated innovative knowledge, bringing new insights and perspectives to clarify the systems biology of liver diseases. A detailed comprehension of epigenetics mechanisms will offer possibilities to develop new therapeutic and diagnostic strategies for NAFLD. Different epigenetic processes have been reported that are modulated by the environment such as gut microbiota, suggesting strong interplays between cellular behavior and pathology. Thus, a more complete description of such mechanisms in hepatic diseases will help to clarify how to control the establishment of fatty liver, and precisely describe molecular interplays that potentially control NAFLD.
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Affiliation(s)
- Letícia F Ramos
- Molecular Biology Laboratory, Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista "Júlio de Mesquita Filho" - Campus Rio Claro, Instituto de Biociências , Rio Claro, Brazil
| | - Caio M Silva
- Molecular Biology Laboratory, Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista "Júlio de Mesquita Filho" - Campus Rio Claro, Instituto de Biociências , Rio Claro, Brazil
| | - Camila C Pansa
- Molecular Biology Laboratory, Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista "Júlio de Mesquita Filho" - Campus Rio Claro, Instituto de Biociências , Rio Claro, Brazil
| | - Karen C M Moraes
- Molecular Biology Laboratory, Departamento de Biologia Geral e Aplicada, Universidade Estadual Paulista "Júlio de Mesquita Filho" - Campus Rio Claro, Instituto de Biociências , Rio Claro, Brazil
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13
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Christoforou ER, Sferruzzi-Perri AN. Molecular mechanisms governing offspring metabolic programming in rodent models of in utero stress. Cell Mol Life Sci 2020; 77:4861-4898. [PMID: 32494846 PMCID: PMC7658077 DOI: 10.1007/s00018-020-03566-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Revised: 05/23/2020] [Accepted: 05/27/2020] [Indexed: 12/13/2022]
Abstract
The results of different human epidemiological datasets provided the impetus to introduce the now commonly accepted theory coined as 'developmental programming', whereby the presence of a stressor during gestation predisposes the growing fetus to develop diseases, such as metabolic dysfunction in later postnatal life. However, in a clinical setting, human lifespan and inaccessibility to tissue for analysis are major limitations to study the molecular mechanisms governing developmental programming. Subsequently, studies using animal models have proved indispensable to the identification of key molecular pathways and epigenetic mechanisms that are dysregulated in metabolic organs of the fetus and adult programmed due to an adverse gestational environment. Rodents such as mice and rats are the most used experimental animals in the study of developmental programming. This review summarises the molecular pathways and epigenetic mechanisms influencing alterations in metabolic tissues of rodent offspring exposed to in utero stress and subsequently programmed for metabolic dysfunction. By comparing molecular mechanisms in a variety of rodent models of in utero stress, we hope to summarise common themes and pathways governing later metabolic dysfunction in the offspring whilst identifying reasons for incongruencies between models so to inform future work. With the continued use and refinement of such models of developmental programming, the scientific community may gain the knowledge required for the targeted treatment of metabolic diseases that have intrauterine origins.
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Affiliation(s)
- Efthimia R Christoforou
- Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge, UK
| | - Amanda N Sferruzzi-Perri
- Department of Physiology, Development and Neuroscience, Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge, UK.
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14
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Qiao R, Di F, Wang J, Wei Y, Zhang Y, Xu T, Wang Y, Gu W, Han B, Yang R. The Association Between RAPSN Methylation in Peripheral Blood and Early Stage Lung Cancer Detected in Case-Control Cohort. Cancer Manag Res 2020; 12:11063-11075. [PMID: 33173339 PMCID: PMC7646459 DOI: 10.2147/cmar.s275321] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 10/03/2020] [Indexed: 12/24/2022] Open
Abstract
Background Early detection is essential to improve the survival and life quality of lung cancer (LC) patients. Changes of peripheral blood DNA methylation could be associated with malignancy but were mostly studied in Caucasians. Methods Here, in a Chinese population, we performed mass spectrometry assays to investigate the association between very early stage LC and methylation levels of RAPSN in the peripheral blood by a case–control cohort using of 221 LC patients (93.2% LC at stage I) and 285 unrelated cancer free control individuals. Results The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using inter-quartile analyses by logistic regression. In general, we observed an association between very early LC and decreased methylation of RAPSN_CpG_1.15 and RAPSN_CpG_3.4 (referring to Q4, OR range from 1.64 to 1.81, p<0.05). Stratified by gender, while hypomethylation of RAPSN_CpG_1.15, RAPSN_CpG_3.4 and RAPSN_CpG_7.14 were associated with LC in males (referring to Q4, ORs range from 1.94 to 2.31, p<0.05), RAPSN_CpG_2 and RAPSN_CpG_5 showed significantly lower methylation in female LC patients comparing to controls (referring to Q4, ORs range from 2.49 to 3.60, p<0.05). The risk of RAPSN hypomethylation to LC was enhanced by aging, and typically for people older than 55 years (referring to Q4, ORs range from 2.17 to 3.61 in six out of all 10 analyzed CpG groups, p<0.05). Conclusion Our study reveals an association between RAPSN hypomethylation in peripheral blood and LC and suggests the occurrence of altered blood-based methylation at the early stage of cancer.
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Affiliation(s)
- Rong Qiao
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China
| | - Feifei Di
- Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China
| | - Jun Wang
- Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China
| | - Yujie Wei
- Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China
| | - Yanman Zhang
- Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China
| | - Tian Xu
- Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210000, People's Republic of China
| | - Yue Wang
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China
| | - Wanjian Gu
- Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210000, People's Republic of China
| | - Baohui Han
- Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China
| | - Rongxi Yang
- Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China.,Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 210000, People's Republic of China
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Berrichi M, Hichami A, Addou-Klouche L, Sayed Khan A, Khan NA. CD36 and GPR120 Methylation Associates with Orosensory Detection Thresholds for Fat and Bitter in Algerian Young Obese Children. J Clin Med 2020; 9:jcm9061956. [PMID: 32585828 PMCID: PMC7356363 DOI: 10.3390/jcm9061956] [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: 05/17/2020] [Revised: 06/16/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022] Open
Abstract
Background: The spontaneous preference for dietary fat is regulated by two lingual lipid sensors (CD36 and GPR120) in humans and rodents. Our objective was to investigate whether obesity in children is associated with methylation of lipid sensor genes, and whether this alteration was implicated in altered gustatory perception of fat and bitter and increased preference of palatable foods. Methods: School children were recruited and classified according to their body mass index (BMI) z-score into two groups: obese and lean children. The detection of orosensory perception for oleic acid and 6-n-propylthiouracil was assessed by using a 3-alternative forced-choice test. After blood DNA extraction, methylation patterns were investigated by methylation-specific PCR. The children were also subjected to a food habit questionnaire. Results: Obese children showed higher lipid and bitter detection thresholds than lean children. Besides, more obese children presented higher methylation level of the CpG sites than lean participants. Interestingly, CD36 and GPR120 gene methylation was associated with high lipid detection thresholds in obese participants. The obese participants preferred highly palatable fat-rich food items, associated with CD36 and GPR120 gene methylation. Conclusion: Epigenetic changes in CD36 and GPR120 genes might contribute to low orosensory perception of fat and bitter taste, and might be, consequently, critically involved in obesity in children
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Affiliation(s)
- Moustafa Berrichi
- Physiologie de la Nutrition & Toxicologie, U1231 INSERM/Université de Bourgogne-Franche Comté (UBFC)/AgroSupDijon, 21000 Dijon, France; (M.B.); (A.H.); (A.S.K.)
- Laboratoire de Biologie Moléculaire Appliquée et Immunologie, Université Abou Bakr Belkaid, Tlemcen 13000, Algeria
| | - Aziz Hichami
- Physiologie de la Nutrition & Toxicologie, U1231 INSERM/Université de Bourgogne-Franche Comté (UBFC)/AgroSupDijon, 21000 Dijon, France; (M.B.); (A.H.); (A.S.K.)
| | - Lynda Addou-Klouche
- Faculté des Science de la Vie et de la Nature, Université Djillali Liabès, Sidi Bel Abbès 22000, Algeria;
| | - Amira Sayed Khan
- Physiologie de la Nutrition & Toxicologie, U1231 INSERM/Université de Bourgogne-Franche Comté (UBFC)/AgroSupDijon, 21000 Dijon, France; (M.B.); (A.H.); (A.S.K.)
| | - Naim Akhtar Khan
- Physiologie de la Nutrition & Toxicologie, U1231 INSERM/Université de Bourgogne-Franche Comté (UBFC)/AgroSupDijon, 21000 Dijon, France; (M.B.); (A.H.); (A.S.K.)
- Correspondence: ; Tel.: +33-3-80-39-63-30-12
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Guo T, Luo F, Lin Q. You are affected by what your parents eat: Diet, epigenetics, transgeneration and intergeneration. Trends Food Sci Technol 2020. [DOI: 10.1016/j.tifs.2020.04.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Dalfrà MG, Burlina S, Del Vescovo GG, Lapolla A. Genetics and Epigenetics: New Insight on Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2020; 11:602477. [PMID: 33335512 PMCID: PMC7736606 DOI: 10.3389/fendo.2020.602477] [Citation(s) in RCA: 85] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 11/02/2020] [Indexed: 12/11/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy, with a prevalence that has increased significantly in the last decade, coming to affect 12-18% of all pregnancies. GDM is believed to be the result of a combination of genetic, epigenetic and environmental factors. Following the identification of susceptibility genes for type 2 diabetes by means of genome-wide association studies, an association has also been demonstrated between some type 2 diabetes susceptibility genes and GDM, suggesting a partial similarity of the genetic architecture behind the two forms of diabetes. More recent genome-wide association studies, focusing on maternal metabolism during pregnancy, have demonstrated an overlap in the genes associated with metabolic traits in gravid and non-gravid populations, as well as in genes apparently unique to pregnancy. Epigenetic changes-such as DNA methylation, histone modifications and microRNA gene silencing-have also been identified in GDM patients. Metabolomics has been used to profile the metabolic state of women during pregnancy, based on the measurement of numerous low-molecular-weight metabolites. Measuring amino acids and conventional metabolites has revealed changes in pregnant women with a higher insulin resistance and high blood glucose levels that resemble the changes seen in non-gravid, insulin-resistant populations. This would suggest similarities in the metabolic profiles typical of insulin resistance and hyperglycemia whether individuals are pregnant or not. Future studies combining data obtained using multiple technologies will enable an integrated systems biology approach to maternal metabolism during a pregnancy complicated by GDM. This review highlights the recent knowledge on the impact of genetics and epigenetics in the pathophysiology of GDM and the maternal and fetal complications associated with this pathology condition.
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Adam AC, Lie KK, Whatmore P, Jakt LM, Moren M, Skjærven KH. Profiling DNA methylation patterns of zebrafish liver associated with parental high dietary arachidonic acid. PLoS One 2019; 14:e0220934. [PMID: 31398226 PMCID: PMC6688801 DOI: 10.1371/journal.pone.0220934] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 07/26/2019] [Indexed: 12/18/2022] Open
Abstract
Diet has been shown to influence epigenetic key players, such as DNA methylation, which can regulate the gene expression potential in both parents and offspring. Diets enriched in omega-6 and deficient in omega-3 PUFAs (low dietary omega-3/omega-6 PUFA ratio), have been associated with the promotion of pathogenesis of diseases in humans and other mammals. In this study, we investigated the impact of increased dietary intake of arachidonic acid (ARA), a physiologically important omega-6 PUFA, on 2 generations of zebrafish. Parental fish were fed either a low or a high ARA diet, while the progeny of both groups were fed the low ARA diet. We screened for DNA methylation on single base-pair resolution using reduced representation bisulfite sequencing (RRBS). The DNA methylation profiling revealed significant differences between the dietary groups in both parents and offspring. The majority of differentially methylated loci associated with high dietary ARA were found in introns and intergenic regions for both generations. Common loci between the identified differentially methylated loci in F0 and F1 livers were reported. We described overlapping gene annotations of identified methylation changes with differential expression, but based on a small number of overlaps. The present study describes the diet-associated methylation profiles across genomic regions, and it demonstrates that parental high dietary ARA modulates DNA methylation patterns in zebrafish liver.
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Affiliation(s)
| | | | | | - Lars Martin Jakt
- Faculty of Biosciences and Aquaculture, Nord University, Bodø, Norway
| | - Mari Moren
- Institute of Marine Research, Bergen, Norway
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Niculite CM, Enciu AM, Hinescu ME. CD 36: Focus on Epigenetic and Post-Transcriptional Regulation. Front Genet 2019; 10:680. [PMID: 31379931 PMCID: PMC6659770 DOI: 10.3389/fgene.2019.00680] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Accepted: 06/28/2019] [Indexed: 12/11/2022] Open
Abstract
CD36 is a transmembrane protein involved in fatty acid translocation, scavenging for oxidized fatty acids acting as a receptor for adhesion molecules. It is expressed on macrophages, as well as other types of cells, such as endothelial and adipose cells. CD36 participates in muscle lipid uptake, adipose energy storage, and gut fat absorption. Recently, several preclinical and clinical studies demonstrated that upregulation of CD36 is a prerequisite for tumor metastasis. Cancer metastasis-related research emerged much later and has been less investigated, though it is equally or even more important. CD36 protein expression can be modified by epigenetic changes and post-transcriptional interference from non-coding RNAs. Some data indicate modulation of CD36 expression in specific cell types by epigenetic changes via DNA methylation patterns or histone tails, or through miRNA interference, but this is largely unexplored. The few papers addressing this topic refer mostly to lipid metabolism-related pathologies, whereas in cancer research, data are even more scarce. The aim of this review was to summarize major epigenetic and post-transcriptional mechanisms that impact CD36 expression in relation to various pathologies while highlighting the areas in need of further exploration.
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Affiliation(s)
- Cristina-Mariana Niculite
- Cell Biology Department, "Victor Babes" National Institute of Pathology, Bucharest, Romania.,Department of Cellular and Molecular Biology and Histology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Ana-Maria Enciu
- Cell Biology Department, "Victor Babes" National Institute of Pathology, Bucharest, Romania.,Department of Cellular and Molecular Biology and Histology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Mihail Eugen Hinescu
- Cell Biology Department, "Victor Babes" National Institute of Pathology, Bucharest, Romania.,Department of Cellular and Molecular Biology and Histology, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
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Zhang Q, Xiao X, Zheng J, Li M, Yu M, Ping F, Wang T, Wang X. A Maternal High-Fat Diet Induces DNA Methylation Changes That Contribute to Glucose Intolerance in Offspring. Front Endocrinol (Lausanne) 2019; 10:871. [PMID: 31920981 PMCID: PMC6923194 DOI: 10.3389/fendo.2019.00871] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 11/28/2019] [Indexed: 12/20/2022] Open
Abstract
Scope: Overnutrition in utero is a critical contributor to the susceptibility of diabetes by programming, although the exact mechanism is not clear. In this paper, we aimed to study the long-term effect of a maternal high-fat (HF) diet on offspring through epigenetic modifications. Procedures: Five-week-old female C57BL6/J mice were fed a HF diet or control diet for 4 weeks before mating and throughout gestation and lactation. At postnatal week 3, pups continued to consume a HF or switched to a control diet for 5 weeks, resulting in four groups of offspring differing by their maternal and postweaning diets. Results: The maternal HF diet combined with the offspring HF diet caused hyperglycemia and insulin resistance in male pups. Even after changing to the control diet, male pups exposed to the maternal HF diet still exhibited hyperglycemia and glucose intolerance. The livers of pups exposed to a maternal HF diet had a hypermethylated insulin receptor substrate 2 (Irs2) gene and a hypomethylated mitogen-activated protein kinase kinase 4 (Map2k4) gene. Correspondingly, the expression of the Irs2 gene decreased and that of Map2k4 increased in pups exposed to a maternal HF diet. Conclusion: Maternal overnutrition programs long-term epigenetic modifications, namely, Irs2 and Map2k4 gene methylation in the offspring liver, which in turn predisposes the offspring to diabetes later in life.
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Moody L, Xu GB, Chen H, Pan YX. Epigenetic regulation of carnitine palmitoyltransferase 1 (Cpt1a) by high fat diet. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS 2018; 1862:141-152. [PMID: 30605728 DOI: 10.1016/j.bbagrm.2018.12.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 12/22/2018] [Accepted: 12/27/2018] [Indexed: 12/15/2022]
Abstract
Carnitine palmitoyltransferase 1 (Cpt1a) is a rate-limiting enzyme that mediates the transport of fatty acids into the mitochondria for subsequent beta-oxidation. The objective of this study was to uncover how diet mediates the transcriptional regulation of Cpt1a. Pregnant Sprague Dawley rats were exposed to either a high-fat (HF) or low-fat control diet during gestation and lactation. At weaning, male offspring received either a HF or control diet, creating 4 groups: lifelong control diet (C/C; n = 12), perinatal HF diet (HF/C; n = 9), post-weaning HF diet (C/HF; n = 10), and lifelong HF diet (HF/HF; n = 10). Only HF/HF animals had higher hepatic Cpt1a mRNA expression than C/C. Epigenetic analysis revealed reduced DNA methylation (DNAMe) and increased histone 3 lysine 4 dimethylation (H3K4Me2) upstream and within the promoter of Cpt1a in the HF/HF group. This was accompanied by increased peroxisome proliferator activated receptor alpha (PPARα) and CCAAT/enhancer binding protein beta (C/EBPβ) binding directly downstream of the Cpt1a transcription start site within the first intron. Findings were confirmed in rat hepatoma H4IIEC3 cells treated with non-esterified fatty acid (NEFA). After 12 h of NEFA treatment, there was an enrichment of SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily D member 1 (BAF60a or SMARCD1) in the first intron of Cpt1a. We conclude that dietary fat elevates hepatic Cpt1a expression via a highly coordinated transcriptional mechanism involving increased H3K4Me2, reduced DNAMe, and recruitment of C/EBPβ, PPARα, PGC1α, and BAF60a to the gene.
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Affiliation(s)
- Laura Moody
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America.
| | - Guanying Bianca Xu
- Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America.
| | - Hong Chen
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America.
| | - Yuan-Xiang Pan
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America; Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States of America; Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, United States of America.
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Molecular Mechanisms Underlying the Link between Diet and DNA Methylation. Int J Mol Sci 2018; 19:ijms19124055. [PMID: 30558203 PMCID: PMC6320837 DOI: 10.3390/ijms19124055] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 12/07/2018] [Accepted: 12/10/2018] [Indexed: 01/07/2023] Open
Abstract
DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation—both hypomethylation and hypermethylation—has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation.
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Rodrigo S, Fauste E, de la Cuesta M, Rodríguez L, Álvarez-Millán JJ, Panadero MI, Otero P, Bocos C. Maternal fructose induces gender-dependent changes in both LXRα promoter methylation and cholesterol metabolism in progeny. J Nutr Biochem 2018; 61:163-172. [PMID: 30236873 DOI: 10.1016/j.jnutbio.2018.08.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 08/03/2018] [Accepted: 08/24/2018] [Indexed: 12/25/2022]
Abstract
Fructose consumption from added sugars correlates with the epidemic rise in obesity, metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. We have investigated whether maternal fructose intake produces subsequent changes in cholesterol metabolism of progeny. Carbohydrates were supplied to pregnant rats in drinking water (10% w/v solution) throughout gestation. Adult male and female descendants from fructose-fed, control or glucose-fed mothers were studied. Male offspring from fructose-fed mothers had elevated plasma HDL-cholesterol levels, whereas female progeny from fructose-fed mothers presented lower levels of non-HDL cholesterol vs. the other two groups. Liver X-receptor (LXR), an important regulator of cholesterol metabolism, and its target genes such as scavenger receptor B1, ATP-binding cassette (ABC)G5 and cholesterol 7-alpha hydroxylase showed decreased gene expression in males from fructose-fed mothers and the opposite in the female progeny. Moreover, the expression of a number of LXRα target genes related to lipogenesis paralleled to that for LXRα expression. In accordance with this, LXRα gene promoter methylation was increased in males from fructose-fed mothers and decreased in the corresponding group of females. Surprisingly, plasma folic acid levels, an important methyl-group donor, were augmented in males from fructose-fed mothers and diminished in female offspring. Maternal fructose intake produces a fetal programming that influences, in a gender-dependent manner, the transcription factor LXRα epigenetically, and both hepatic mRNA gene expression and plasma parameters of cholesterol metabolism in adult progeny. Changes in the LXRα promoter methylation might be related to the availability of the methyl donor folate.
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Affiliation(s)
- Silvia Rodrigo
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | - Elena Fauste
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | - Maite de la Cuesta
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | - Lourdes Rodríguez
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | | | - María I Panadero
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | - Paola Otero
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain
| | - Carlos Bocos
- Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Montepríncipe, Boadilla del Monte, Madrid, Spain.
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24
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Andraos S, de Seymour JV, O'Sullivan JM, Kussmann M. The Impact of Nutritional Interventions in Pregnant Women on DNA Methylation Patterns of the Offspring: A Systematic Review. Mol Nutr Food Res 2018; 62:e1800034. [PMID: 30035846 DOI: 10.1002/mnfr.201800034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 07/12/2018] [Indexed: 12/14/2022]
Abstract
Epidemiological studies have consistently demonstrated that environmental exposures in early life are associated with later-life health status and disease susceptibility. Epigenetic modifications, such as DNA methylation, have been suggested as potential mechanisms linking the intrauterine environment with offspring health status. The present systematic review compiles peer-reviewed randomized controlled trials assessing the impact of maternal nutritional interventions on DNA methylation patterns of the offspring. The results of the included trials are consistent with micronutrient supplementation not significantly affecting offspring tissue DNA methylation patterns, yet subgrouping by sex, BMI, and smoking status increased the significance of nutritional supplementation on DNA methylation. Maternal BMI and smoking status as well as offspring sex were factors influencing offspring DNA methylation responsiveness to nutritional interventions during pregnancy. Future research should aim at assessing the impact of nutritional interventions on DNA methylation patterns of neonates comparing single versus multi-micronutrient supplementation, within populations having high versus low baseline nutritional statuses.
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Affiliation(s)
- Stephanie Andraos
- The Liggins Institute, Faculty of Medical and Health Sciences, The University of Auckland, 1023, Auckland, New Zealand
| | - Jamie Violet de Seymour
- The Liggins Institute, Faculty of Medical and Health Sciences, The University of Auckland, 1023, Auckland, New Zealand
| | - Justin Martin O'Sullivan
- The Liggins Institute, Faculty of Medical and Health Sciences, The University of Auckland, 1023, Auckland, New Zealand
| | - Martin Kussmann
- The Liggins Institute, Faculty of Medical and Health Sciences, The University of Auckland, 1023, Auckland, New Zealand.,New Zealand National Science Challenge, High-Value Nutrition, The University of Auckland, 1023, Auckland, New Zealand
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25
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Seidah NG, Chrétien M, Mbikay M. The ever-expanding saga of the proprotein convertases and their roles in body homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9 functions and regulation. Curr Opin Lipidol 2018; 29:144-150. [PMID: 29342010 DOI: 10.1097/mol.0000000000000484] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW The nine members of the proprotein convertase family play major physiological roles during development and in the adult, and their dysregulation leads to various diseases. The primary objective of this article is to review recent findings on the clinical importance of some of these convertases concentrating mostly on PCSK9, the ninth member of the convertase family. This includes the transcriptional and translational regulation of PCSK9, its ability to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9 in inflammation and sepsis. RECENT FINDINGS PCSK9 levels are upregulated by E2F1 and reduced by specific miRNAs and by Annexin A2 that bind the 3' end of its mRNA. The implication of the LDLR in the clearance of pathogenic bacterial debris in mice and human puts in perspective a new role for PCSK9 in the regulation of sepsis. The specific implication of the LDLR in the clearance of Lp(a) is now confirmed by multiple studies of PCSK9 inhibition in human cohorts. SUMMARY Emerging data suggest that PCSK9 can be regulated at the transcriptional and translational levels by specific factors and miRNAs. The identification of a novel pocket in the catalytic domain of PCSK9 represents a harbinger for a new class of small inhibitor drugs. The implication of the LDLR in reducing the effects of bacterially induced sepsis has been supported by both human and mouse data. Outcome studies confirmed the clinical importance of reducing PCSK9 levels. The present review puts in perspective new developments in the PCSK9 biology and its regulation of the LDLR. VIDEO ABSTRACT: http://links.lww.com/COL/A17.
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Affiliation(s)
| | - Michel Chrétien
- Laboratory of Functional Endoproteolysis, Montreal Clinical Research Institute of Montreal (IRCM), Montreal, Quebec, Canada
| | - Majambu Mbikay
- Laboratory of Functional Endoproteolysis, Montreal Clinical Research Institute of Montreal (IRCM), Montreal, Quebec, Canada
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26
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Moody L, Chen H, Pan YX. Postnatal diet remodels hepatic DNA methylation in metabolic pathways established by a maternal high-fat diet. Epigenomics 2017; 9:1387-1402. [DOI: 10.2217/epi-2017-0066] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim: We investigate how postweaning diet may modify the epigenetic landscape to meet metabolic demands later in life. Methods: Sprague-Dawley rats were exposed to a high-fat (HF) diet during gestation and lactation. At weaning, male offspring were placed either on an HF diet (HF/HF) or a control diet (HF/C). Methylation-dependent immunoprecipitation sequencing and methylation-sensitive restriction enzyme sequencing were used to quantify hepatic DNA methylation. Results: Out of the 3966 identified differentially methylated regions, 37% were mapped to gene bodies while 6% fell within promoter or downstream regions. Differentially methylated genes were clustered in the type II diabetes mellitus and the adipocytokine signaling pathways. Conclusion: Our results indicate that compared with a lifelong HF diet, offspring exposed to a new postweaning control diet are able to remodel the hepatic epigenome, emphasizing the dynamic nature of the methylome even after early life.
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Affiliation(s)
- Laura Moody
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Hong Chen
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Food Science & Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
| | - Yuan-Xiang Pan
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Department of Food Science & Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
- Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
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27
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Kereliuk SM, Brawerman GM, Dolinsky VW. Maternal Macronutrient Consumption and the Developmental Origins of Metabolic Disease in the Offspring. Int J Mol Sci 2017; 18:E1451. [PMID: 28684678 PMCID: PMC5535942 DOI: 10.3390/ijms18071451] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2017] [Revised: 06/14/2017] [Accepted: 06/30/2017] [Indexed: 12/18/2022] Open
Abstract
Recent research aimed at understanding the rise in obesity and cardiometabolic disease in children suggests that suboptimal maternal nutrition conditions organ systems and physiological responses in the offspring contributing to disease development. Understanding the mechanisms by which the macronutrient composition of the maternal diet during pregnancy or lactation affects health outcomes in the offspring may lead to new maternal nutrition recommendations, disease prevention strategies and therapies that reduce the increasing incidence of cardiometabolic disease in children. Recent mechanistic animal model research has identified how excess fats and sugars in the maternal diet alter offspring glucose tolerance, insulin signaling and metabolism. Maternal nutrition appears to influence epigenetic alterations in the offspring and the programming of gene expression in key metabolic pathways. This review is focused on experimental studies in animal models that have investigated mechanisms of how maternal consumption of macronutrients affects cardiometabolic disease development in the offspring. Future research using "-omic" technologies is essential to elucidate the mechanisms of how altered maternal macronutrient consumption influences the development of disease in the offspring.
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Affiliation(s)
- Stephanie M Kereliuk
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
| | - Gabriel M Brawerman
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
| | - Vernon W Dolinsky
- Department of Pharmacology & Therapeutics, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
- Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme of the Children's Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
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28
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Park JH, Kim SH, Lee MS, Kim MS. Epigenetic modification by dietary factors: Implications in metabolic syndrome. Mol Aspects Med 2017; 54:58-70. [PMID: 28216432 DOI: 10.1016/j.mam.2017.01.008] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 12/26/2016] [Accepted: 01/03/2017] [Indexed: 02/06/2023]
Abstract
Dietary factors play a role in normal biological processes and are involved in the regulation of pathological progression over a lifetime. Evidence has emerged indicating that dietary factor-dependent epigenetic modifications can significantly affect genome stability and the expression of mRNA and proteins, which are involved in metabolic dysfunction. Since metabolic syndrome is a progressive phenotype characterized by insulin resistance, obesity, hypertension, dyslipidemia, or type 2 diabetes, gene-diet interactions are important processes involved in the initiation of particular symptoms of metabolic syndrome and their progression. Some epigenetic risk markers can be initiated or reversed by diet and environmental factors. In this review, we discuss recent advances in our understanding of the interactions between dietary factors and epigenetic changes in metabolic syndrome. We discuss the contribution of nutritional factors in transgenerational inheritance of epigenetic markers and summarize the current knowledge of epigenetic modifications by dietary bioactive components in metabolic diseases. The intake of dietary components that regulate epigenetic modifications can provide significant health effects and, as an epigenetic diet, may prevent various pathological processes in the development of metabolic disease.
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Affiliation(s)
- Jae-Ho Park
- Division of Metabolism and Nutrition, Korea Food Research Institute, Gyeonggi-do 13539, Republic of Korea; Department of Food Biotechnology, Korea University of Science & Technology, Gyeonggi-do 13539, Republic of Korea
| | - Soon-Hee Kim
- Division of Metabolism and Nutrition, Korea Food Research Institute, Gyeonggi-do 13539, Republic of Korea
| | - Myeong Soo Lee
- Clinical Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea
| | - Myung-Sunny Kim
- Division of Metabolism and Nutrition, Korea Food Research Institute, Gyeonggi-do 13539, Republic of Korea; Department of Food Biotechnology, Korea University of Science & Technology, Gyeonggi-do 13539, Republic of Korea.
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29
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McKay JA, Xie L, Adriaens M, Evelo CT, Ford D, Mathers JC. Maternal folate depletion during early development and high fat feeding from weaning elicit similar changes in gene expression, but not in DNA methylation, in adult offspring. Mol Nutr Food Res 2017; 61. [DOI: 10.1002/mnfr.201600713] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Revised: 11/21/2016] [Accepted: 11/21/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Jill A. McKay
- Human Nutrition Research Centre; Institute for Health and Society; Newcastle University; UK
| | - Long Xie
- Human Nutrition Research Centre, Institute of Cellular Medicine; Newcastle University; UK
| | - Michiel Adriaens
- Maastricht Centre for Systems Biology; Maastricht The Netherlands
| | - Chris T. Evelo
- Department of Bioinformatics - BiGCaT; Maastricht University; Maastricht The Netherlands
| | - Dianne Ford
- Human Nutrition Research Centre, Institute for Cell and Molecular Biosciences; Newcastle University; UK
- Faculty of Health and Life Sciences; Northumbria University; UK
| | - John C. Mathers
- Human Nutrition Research Centre, Institute of Cellular Medicine; Newcastle University; UK
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30
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Bogsrud MP, Ulven SM, Holven KB. Does intrauterine exposure to hypercholesterolemia adversely affect familial hypercholesterolemia phenotype? Curr Opin Lipidol 2016; 27:382-7. [PMID: 27070077 DOI: 10.1097/mol.0000000000000299] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW There is currently limited information as to whether maternally or paternally inherited familial hypercholesterolemia confers different phenotype risk to offspring. Knowledge about the differences in risk conferred by inheritance could be important with respect to follow-up and more individually targeted treatment of subjects with familial hypercholesterolemia. RECENT FINDINGS Few studies have, with inconsistent results so far, investigated the significance of familial hypercholesterolemia inheritance on cardiovascular risk markers in offspring. Maternal inheritance of familial hypercholesterolemia includes hypercholesterolemic in-utero conditions for the offspring. How this may influence later risk is briefly discussed in the article. SUMMARY Current data suggest that the dominating factor of the familial hypercholesterolemia (FH) phenotype is the mutation and not the inheritance, however, maternal inheritance of FH has been reported to adversely affect FH phenotype in terms of increased mortality. More knowledge about how intrauterine hypercholesterolemia during pregnancy influences epigenetic modifications and later cardiovascular disease risk in offspring is needed and this may open up new avenues of treatment of pregnant women with familial hypercholesterolemia.
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Affiliation(s)
- Martin P Bogsrud
- aDepartment of Endocrinology, Morbid Obesity, and Preventive Medicine, Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital bDepartment of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
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31
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Jiao F, Yan X, Yu Y, Zhu X, Ma Y, Yue Z, Ou H, Yan Z. Protective effects of maternal methyl donor supplementation on adult offspring of high fat diet-fed dams. J Nutr Biochem 2016; 34:42-51. [DOI: 10.1016/j.jnutbio.2016.04.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2015] [Revised: 04/21/2016] [Accepted: 04/22/2016] [Indexed: 01/05/2023]
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32
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Hocher B, Haumann H, Rahnenführer J, Reichetzeder C, Kalk P, Pfab T, Tsuprykov O, Winter S, Hofmann U, Li J, Püschel GP, Lang F, Schuppan D, Schwab M, Schaeffeler E. Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner. Epigenetics 2016; 11:539-52. [PMID: 27175980 PMCID: PMC4939931 DOI: 10.1080/15592294.2016.1184800] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.
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Affiliation(s)
- Berthold Hocher
- a Department of Basic Medicine , Medical College of Hunan Normal University , Changsha , China.,b Institute of Nutritional Science, University of Potsdam , Nuthetal , Germany.,c IFLb, Laboratoriumsmedizin Berlin GmbH , Berlin , Germany
| | - Hannah Haumann
- d Department of Internal Medicine IV/Nephrology (UKBF) , Charité Campus Benjamin Franklin , Berlin , Germany.,e Center for Cardiovascular Research, Charité Campus Mitte , Berlin , Germany
| | - Jan Rahnenführer
- b Institute of Nutritional Science, University of Potsdam , Nuthetal , Germany
| | | | - Philipp Kalk
- d Department of Internal Medicine IV/Nephrology (UKBF) , Charité Campus Benjamin Franklin , Berlin , Germany.,e Center for Cardiovascular Research, Charité Campus Mitte , Berlin , Germany
| | - Thiemo Pfab
- d Department of Internal Medicine IV/Nephrology (UKBF) , Charité Campus Benjamin Franklin , Berlin , Germany.,f Diaverum Deutschland , Potsdam , Germany
| | - Oleg Tsuprykov
- b Institute of Nutritional Science, University of Potsdam , Nuthetal , Germany.,e Center for Cardiovascular Research, Charité Campus Mitte , Berlin , Germany
| | - Stefan Winter
- g Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology , Stuttgart , Germany.,h University of Tübingen , Tübingen , Germany
| | - Ute Hofmann
- g Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology , Stuttgart , Germany.,h University of Tübingen , Tübingen , Germany
| | - Jian Li
- a Department of Basic Medicine , Medical College of Hunan Normal University , Changsha , China
| | - Gerhard P Püschel
- b Institute of Nutritional Science, University of Potsdam , Nuthetal , Germany
| | - Florian Lang
- i Institute of Physiology, University of Tübingen , Tübingen , Germany
| | - Detlef Schuppan
- j Institute of Translational Immunology, University Medical Center of the Johannes Gutenberg University Mainz , Mainz , Germany.,k Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , MA , USA
| | - Matthias Schwab
- g Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology , Stuttgart , Germany.,l Department of Clinical Pharmacology , University Hospital Tübingen , Tübingen , Germany.,m Department of Pharmacy and Biochemistry , University Tübingen , Tübingen , Germany
| | - Elke Schaeffeler
- g Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology , Stuttgart , Germany.,h University of Tübingen , Tübingen , Germany
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33
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Zhang N. Epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals. ACTA ACUST UNITED AC 2015; 1:144-151. [PMID: 29767106 PMCID: PMC5945948 DOI: 10.1016/j.aninu.2015.09.002] [Citation(s) in RCA: 90] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 09/01/2015] [Indexed: 12/21/2022]
Abstract
It is well known that phenotype of animals may be modified by the nutritional modulations through epigenetic mechanisms. As a key and central component of epigenetic network, DNA methylation is labile in response to nutritional influences. Alterations in DNA methylation profiles can lead to changes in gene expression, resulting in diverse phenotypes with the potential for decreased growth and health. Here, I reviewed the biological process of DNA methylation that results in the addition of methyl groups to DNA; the possible ways including methyl donors, DNA methyltransferase (DNMT) activity and other cofactors, the critical periods including prenatal, postnatal and dietary transition periods, and tissue specific of epigenetic modulation of DNA methylation by nutrition and its mechanisms in animals.
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Affiliation(s)
- Naifeng Zhang
- Feed Research Institute of Chinese Academy of Agricultural Sciences, Key Laboratory of Feed Biotechnology of the Ministry of Agriculture, Beijing 100081, China
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