The Role of Epigenetics in the Development of Human Obesity and Type 2 Diabetes: A Review
Keywords:
Epigenetics, Obesity, DNA Methylation,, Type 2 Diabetes, Histone Modifications, Disease, Non-coding RNAsAbstract
Epigenetic mechanisms control gene exertion and the development of an organism. It is the epigenetic imprints that instruct cells to respond reversibly to environmental factors and keep the specific gene stable in an organism’s lifetime. It has been established that the human epigenome includes DNA methylation, histone modifications, and RNA-mediated processes, and disturbance of this balance may beget several pathologies and contribute to the development of human obesity and type 2 diabetes (T2D). This Review is aimed at recapitulating the functional roles played by epigenetic via DNA methylation, histone modifications, and RNA-mediated processes in relation to obesity and type 2 diabetes. Since this research field is still young, these comprehensive data have only supported part of epigenetics in disease or complaint development, and also epigenetic differences as a response to disease. The reversible nature of epigenetic variations holds promise for future therapeutic and remedial strategies in obesity and type 2 diabetes, hence, further studies on the subject matter is highly recommended.
References
. S. .O. Oguche, "Evaluation of Renoprotective Potential of Plantain (Musa parasidiaca) Stem Juice on Rat Model Diabetes", International Journal of Scientific Research in Chemical Sciences, Vol.8, Issue 5, pp.11-15, 2021.
. L.U. Onah, S.O. Oguche, "Histopathological Analysis of the Kidney of Alloxan Induced Diabetic Albino (Wistar Strain) Rat Treated with Musa paradisiaca (Plantain) Stem Juice", International Journal of Scientific Research in Chemical Sciences, Vol.9, Issue 2, pp.08-13, 2022.
. A.M. Mahmoud, "An Overview of Epigenetics in Obesity: The Role of Lifestyle and Therapeutic Interventions", Int. J. Mol. Sci., Vol.23, Issue 1341, pp.01-22, 2022.
. H.C. Ogbonna, S.O. Oguche, "Investigation into the Lipidemic Potential of Musa paradisiaca (Plantain) Stem Juice in Alloxan Induced Diabetic Wistar Rats", International Journal of Scientific Research in Chemical Sciences, Vol.9, Issue 1, pp.01-05, 2022.
. M.A. Gammone, N. D’Orazio, "COVID-19 and Obesity: Overlapping of Two Pandemics", Obes. Facts, Vol.14, pp.579–585, 2021.
. Y.J. Park, S.M. Han, J.B. Huh, J.Y.; Kim, "Emerging Roles of Epigenetic Regulation in Obesity and Metabolic Disease", J. Biol. Chem., Vol.297, pp.101296, 2021.
. S.T. Keating, and A. El-Osta, "Epigenetics and Metabolism", Circ. Res, Vol.116, pp.715-736, 2015.
. T. Zhang, S. Cooper, N. Brockdorff, "The Interplay of Histone Modifications Writers that Read", EMBO Rep, Vol.16, pp.1467-1481, 2015.
. E. Agardh, A. Lundstig, A. Perfilyev, P. Volkov, T. Freiburghaus, E. Lindholm, T. Rönn, C.D. Agardh, C. Ling, "Genome-wide Analysis of DNA Methylation in Subjects with Type 1 Diabetes Identifies Epigenetic Modifications Associated with Proliferative Diabetic Retinopathy", BMC Med, Vol.13, p.182, 2015.
. S. Karachanak-Yankova, R. Dimova, D. Nikolova, D. Nesheva, M. Koprinarova, S. Maslyankov, "Epigenetic Alterations in Patients with Type 2 Diabetes Mellitus", Balkan Journal of Medical Genetics, Vol.18, pp.15-24, 2015.
. E. Hall, P. Volkov, T. Dayeh, K. Bacos, T. Ronn, M.D. Nitert, C. Ling, "Effects of Palmitate on Genome-wide mRNA Expression and DNA Methylation Patterns in Human Pancreatic Islets", BMC Med, Vol.12, p.103, 2014.
. N.H.Cho, J.E. Shaw, S. Karuranga Y. Huang, J.D. da Rocha, Fernandes A.W. Ohlrogge, B. Malanda, "IDF Diabetes Atlas: Global Estimates of Diabetes Prevalence for 2017 and Projections for 2045", Diabetes Res. Clin. Pract, Vol.138, pp.271-281, 2017.
. L. Yengo, J. Sidorenko, "Meta-analysis of Genome-wide Association Studies for Height and Body Mass Index in ?700000 Individuals of European Ancestry" Hum. Mol. Genet, Vol.27, pp.3641-3649, 2018.
. A. Mahajan, D. Taliun, D. "Fine-mapping Type 2 Diabetes Loci to Single-variant Resolution Using High-density Imputation and Islet-specific Epigenome Maps", Nat. Genet, Vol.50, pp.1505-1513, 2018.
. A.E. Locke, B. Kahali "Genetic Studies of Body Mass Index Yield New Insights for Obesity Biology", Nature, Vol.518, pp.197-200, 2015.
. I. Barroso, M.I. McCarthy, "The Genetic Basis of Metabolic Disease", Cell, Vol.177, pp.146-161, 2019.
. N.J. Pillon, R.J.F. Loos, "Metabolic Consequences of Obesity and Type 2 Diabetes: Balancing Genes and Environment for Personalized Care", Cell, Vol.184, pp.1530-1544, 2021.
. M. Arif, S. Sadayappan, R.C. Becker "Epigenetic modification: A Regulatory Mechanism in Essential Hypertension", Hypertension Research, Vol.42, pp.1099-1113, 2019.
. A.A. Rasha, T. Heinbockel, A. B. Csoka, "Epigenetics to Optogenetics - A New Paradigm in the Study of Biology", IntechOpen, 2022. DOI:
. Y. Ji, A.M. Yiorkas, "Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension", Diabetes, Vol.68, pp.207-219, 2019.
. E. Hall, M. Dekker, Nitert, P. Volkov, S. Malmgren, H. Mulder, K. Bacos, C. Ling, "The Effects of High Glucose Exposure on Global Gene Expression and DNA Methylation in Human Pancreatic Islets", Mol. Cell. Endocrinol, Vol.472, pp.57-67, 2018.
. M. Nakatochi, S. Ichihara, K. Yamamoto, K. Naruse, S. Yokota, H. Asano, T. Matsubara, M. Yokota, "Epigenome-wide Association of Myocardial Infarction with DNA Methylation Sites at Loci Related to Cardiovascular Disease", Clin. Epigenetics, Vol.9, p.54, 2017
. E.W. Demerath, W. Guan, M.L. Grove, S. Aslibekyan, M. Mendelson, Y.H. Zhou, A.K. Hedman, J.K. Sandling, L.A. Li, M.R. Irvin, "Epigenome-wide Association Study (EWAS) of BMI, BMI Change and Waist Circumference in African American Adults Identifies Multiple Replicated Loci", Hum. Mol. Genet, Vol.24, pp.4464-4479, 2015.
. P. Petrus, L. Bialesova, A. Checa, A. Kerr, S. Naz, J. Backdahl, A. Gracia, S. Toft, K. Dahlman-Wright, P. Heden, "Adipocyte Expression of SLC19A1 Links DNA Hypermethylation to Adipose Tissue Inflammation and Insulin Resistance", J. Clin. Endocrinol. Metab, Vol.103, pp.710–721, 2018.
. M.A.S. Pinhel, N.Y. Noronha, C.F. Nicoletti, V.A. Pereira, B.A. de Oliveira, C. Cortes-Oliveira, W. Salgado, Jr. Barbosa, Jr. Marchini, J.S. Souza, "Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass", Int. J. Mol. Sci, Vol.21, p.4476, 2020.
. A. Sadashiv; M. Modi, P. Khokhar, R. Sharma, S.S. Joshi, R.N. Mishra, S. Bharshankar, Tiwari, P.K. Singh, V.V. Bhosale, "Leptin DNA Methylation and Its Association with Metabolic Risk Factors in a Northwest Indian Obese Population", J. Obes. Metab. Syndr, Vol.30, pp.304–311, 2021.
. D. You, E. Nilsson, D.E. Tenen, A. Lyubetskaya, J.C. Lo, R. Jiang, J. Deng, B.A. Dawes, A. Vaag, C. Ling, "Dnmt3a is an Epigenetic Mediator of Adipose Insulin Resistance", Elife, Vol.6, p.30766, 2017.
. M.M. Ali, C. Hassan, M. Masrur, F.M. Bianco, D. Naquiallah, I. Mirza, P. Frederick, E.T. Fernandes, C.P. Giulianotti, A. Gangemi, "Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction", Biomedicines, Vol.9, p.1034, 2021.
. X. Ma, S. Kang, "Functional Implications of DNA Methylation in Adipose Biology", Diabetes, Vol.68, pp.871–878, 2019.
. J. Castillo, G. Lopez-Rodas, L. Franco, "Histone Post-Translational Modifications and Nucleosome Organisation in Transcriptional Regulation: Some Open Questions", Adv. Exp. Med. Biol., Vol.966, pp.65–92, 2017.
. H. Yang, K. Yang, H. Gu, C. Sun, "Dynamic POST-translational Modifications in Obesity", J. Cell Mol. Med., Vol.24, pp.2384–2387, 2020.
. J.F. Landrier, A. Derghal, L. Mounien, "MicroRNAs in Obesity and Related Metabolic Disorders", Cells, Vol.8, p.859, 2019.
. J. Sun, Y. Ruan, M. Wang, R. Chen, N. Yu, L. Sun, T. Liu, H. Chen, "Differentially Expressed Circulating LncRNAs and mRNA Identified by Microarray Analysis in Obese Patients", Sci. Rep, Vol.6, p.35421, 2016.
. C. Ding, Y.C. Lim, S.Y. Chia, A.C.E. Walet, S. Xu, K.A. Lo, Y. Zhao, D. Zhu, Z. Shan, Q. Chen, "De novo Reconstruction of Human Adipose Transcriptome Reveals Conserved lncRNAs as Regulators of Brown Adipogenesis", Nat. Commun, Vol.9, p.1329, 2018.
. K. Stapleton, S. Das, M.A. Reddy, A. Leung, V. Amaram, L. Lanting, Z. Chen, L. Zhang, R. Palanivel, J.A. Deiuliis, "Novel Long Noncoding RNA, Macrophage Inflammation-Suppressing Transcript (MIST), Regulates Macrophage Activation During Obesity", Arterioscler. Thromb. Vasc. Biol, Vol.40, pp.914–928, 2020.
. T. Squillaro, G. Peluso, U. Galderisi, G. Di Bernardo, "Long Non-coding RNAs in Regulation of Adipogenesis and Adipose Tissue Function", Elife, Vol.9, p.59053, 2020
. M. Arif, S. Sadayappan, R.C. Becker, "Epigenetic Modification: A Regulatory Mechanism in Essential Hypertension", Hypertension Research, Vol.42, pp.1099-1113, 2019.
. S. Karachanak-Yankova, R. Dimova, D. Nikolova, D. Nesheva, M. Koprinarova, S. Maslyankov, "Epigenetic Alterations in Patients with Type 2 Diabetes Mellitus", Balkan Journal of Medical Genetics, Vol.18, pp.15-24, 2015.
. S Sestakova C. Salek, H. Remesova, "DNA Methylation Validation Methods: A Coherent Review with Practical Comparison", Biol. Proced. Online, Vol.21, p.19, 2019.
. S. Karachanak-Yankov, R. Dimova, D. Nikolova, D. Nesheva, M. Koprinarova, S. Maslyankov S, "Epigenetic Alterations in Patients with Type 2 Diabetes Mellitus", Balkan Journal of Medical Genetics, Vol.18, pp.15-24, 2015.
. G.A. Raciti, M. Longo, "Understanding Type 2 Diabetes: From Genetics to Epigenetics", Acta Diabetol., Vol.52, pp.821–827, 2015.
. A. Abderrahmani, L. Yengo, "Increased Hepatic PDGF-AA Signaling Mediates Liver Insulin Resistance in Obesity-Associated Type 2 Diabetes", Diabetes, Vol.67, pp.1310–1321, 2018.
. E.D. Rosen, K.H. Kaestner, "Epigenetics and Epigenomics: Implications for Diabetes and Obesity", Diabetes, Vol.67, pp.1923–1931, 2018.
. G.C. Sharp, D.A. Lawlor, R.C. Richmond, A. Fraser, A. Simpkin, M. Suderman, H.A. Shihab, O. Lyttleton, W. McArdle, S.M. Ring, "Maternal Pre-pregnancy BMI and Gestational Weight Gain, Offspring DNA Methylation and Later Offspring Adiposity: Findings from the Avon Longitudinal Study of Parents and Children", Int. J. Epidemiol, Vol.44, pp.1288-1304, 2015.
. C. Allard, V. Desgagne, J. Patenaude, M. Lacroix, L. Guillemette, M.C. Battista, M. Doyon, J., Menard, J.L. Ardilouze, P. Perron, "Mendelian Randomization Supports Causality between Maternal Hyperglycemia and Epigenetic Regulation of Leptin Gene in Newborns", Epigenetics, Vol.10, pp.342-351, 2015.
. I. Dahlman, I. Sinha, "The Fat Cell Epigenetic Signature in Post-obese Women is Characterized by Global Hypomethylation and Differential DNA Methylation of Adipogenesis Genes", Int. J. Obes., Vol.39, pp.910–919, 2015.
. I. Donkin, S. Versteyhe, L.R. Ingerslev, K. Qian, M. Mechta, L. Nordkap, B. Mortensen, E.V. Appel, N. Jorgensen, V.B. Kristiansen, "Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans", Cell Metab, Vol.23, pp.369-378, 2016.
. I. Donkin, R. Barres, "Sperm Epigenetics and Influence of Environmental Factors", Mol. Metab, Vol.14, pp.1-11, 2018.
. M.F. Perez, B. Lehner, "Intergenerational and Transgenerational Epigenetic Inheritance in Animals", Nat. Cell Biol, Vol.21, pp.143-151, 2019.
. K. Trang, S.F. Grant, “Genetics and epigenetics in the obesity phenotyping scenario”, Rev Endocr Metab Disord, 2023. https://doi.org/10.1007/s11154-023-09804-6
. A. Onrust-van, S. Marjolein, J.W. de Bruijn, B. S. Rutger, W.W. Brouwer, G.J. Braunstahl, F.J. Wilfred, V. Icken, T. Graf, D. Huylebroeck, W. Rudi, H. G. Stik, R. Stadhouders. “3D Chromatin Reprogramming Primes Human Memory T H 2 Cells for Rapid Recall and Pathogenic Dysfunction”, Science Immunology, Vol.8, Isuue.85, 2023. DOI:
. S. Albert, A. D. Al-Rawi, B. Dameracharla, R. Raviram, S. C. L. Bailey, S. Stransky, L. Scipioni, J. Luebeck, M. Di Bona, D. Norkunaite, M. R. Myers, M. Duran, S. Choi, B. Weigelt, S. Yomtoubian, A. McPherson, E. Toufektchan, K. Keuper, S. Paul, V. Mittal, P. Sohrab, Shah, J. Maciejowski, Z. Storchova, E. Gratton, P. Ly, D. Landau, M. F. Bakhoum, R. P. Koche, S. Sidoli, V. Bafna, Y. David, S. F. Bakhoum. “Epigenetic Dysregulation from Chromosomal Transit in Micronuclei”, Nature, 2023; DOI: 10.1038/s41586-023-06084-7
. A. K. Ruehlmann, S. Sammallahti, P. Andrea, C. Hidalgo, K. M. Bakulski, E. B. Binder, M. L. Campbell, D. Caramaschi, A. Charlotte, A. M. Cecil, E. Colicino, C. Cruceanu, D. Czamara, L. Dieckmann, J. Dou, J. F. Felix, J. Frank, S. E. Håberg, G. Herberth, T. Thanh, Hoang, Lotte C. Houtepen, Anke Hüls, Nastassja Koen, Stephanie J. London, Maria C. Magnus, Giulia Mancano, Rosa H. Mulder, M. Christia, K. Räikkönen, S. Röder, R. J. Schmidt, T. S. Send, G. Sharp, D. J. Stein, F. Streit, J. Tuhkanen, S. H. Witt, H. J. Zar, A. C. Zenclussen, Y. Zhang, L. Zillich, R. Wright, J. Lahti, K. J. Brunst. “Epigenome-wide META-analysis of Prenatal Maternal Stressful Life Events and Newborn DNA Methylation”, Molecular Psychiatry, 2023; DOI: 10.1038/s41380-023-02010-5
. E. Dror, L. Fagnocchi, V. Wegert, S. Apostle, B. Grimaldi, T. Gruber, I. Panzeri, S. Heyne, K. D. Höffler, V. Kreiner, R. Ching, T. T. Lu, A. Semwal, B. Johnson, P. Senapati, A. Lempradl, D. Schones, A. Imhof, H. Shen, J. A. Pospisilik. “Epigenetic Dosage Identifies Two Major and Functionally Distinct ? Cell Subtypes”, Cell Metabolism, 2023; DOI: 10.1016/j.cmet.2023.03.008
. S. Schrader, A. Perfilyev, E. Ahlqvist, L. Groop, A. Vaag, M. Martinell, S. García-Calzón, C. Ling. “Novel Subgroups of Type 2 Diabetes Display Different Epigenetic Patterns, Which Associate With Future Diabetic Complications”, Diabetes Care, 2022; DOI: 10.2337/dc21-2489
. S. Wahl, A. Drong, "Epigenome-wide Association Study of Body Mass Index, and the Adverse Outcomes of Adiposity", Nature, Vol.541, pp.81–86, 2016.
. Y. Ji, A.M. Yiorkas, "Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension", Diabetes, Vol.68, pp.207–219, 2019.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors contributing to this journal agree to publish their articles under the Creative Commons Attribution 4.0 International License, allowing third parties to share their work (copy, distribute, transmit) and to adapt it, under the condition that the authors are given credit and that in the event of reuse or distribution, the terms of this license are made clear.
