Sangeeta Dhawan1, Rama Natarajan2. 1. Department of Translational Research and Cellular Therapeutics, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. 2. Department of Diabetes Complications and Metabolism, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. rnatarajan@coh.org.
Abstract
PURPOSE OF REVIEW: The influence of environmental factors on type 2 diabetes (T2D) risk is now well recognized and highlights the contribution of epigenetic mechanisms. This review will focus on the role of epigenetic factors in the risk and pathogenesis of T2D. RECENT FINDINGS: Epigenetic dysregulation has emerged as a key mechanism underpinning the pathogenesis of T2D and its complications. Environmental variations, including alterations in lifestyle, nutrition, and metabolic demands during prenatal and postnatal life can induce epigenetic changes that may impact glucose homeostasis and the function of different metabolic organs. Accumulating data continues to uncover the specific pathways that are epigenetically dysregulated in T2D, providing an opportunity for therapeutic targeting. Environmental changes can disrupt specific epigenetic mechanisms underlying metabolic homeostasis, thus contributing to T2D pathogenesis. Such epigenetic changes can be transmitted to the next generation, contributing to the inheritance of T2D risk. Recent advances in epigenome-wide association studies and epigenetic editing tools present the attractive possibility of identifying epimutations associated with T2D, correcting specific epigenetic alterations, and designing novel epigenetic biomarkers and interventions for T2D.
PURPOSE OF REVIEW: The influence of environmental factors on type 2 diabetes (T2D) risk is now well recognized and highlights the contribution of epigenetic mechanisms. This review will focus on the role of epigenetic factors in the risk and pathogenesis of T2D. RECENT FINDINGS: Epigenetic dysregulation has emerged as a key mechanism underpinning the pathogenesis of T2D and its complications. Environmental variations, including alterations in lifestyle, nutrition, and metabolic demands during prenatal and postnatal life can induce epigenetic changes that may impact glucose homeostasis and the function of different metabolic organs. Accumulating data continues to uncover the specific pathways that are epigenetically dysregulated in T2D, providing an opportunity for therapeutic targeting. Environmental changes can disrupt specific epigenetic mechanisms underlying metabolic homeostasis, thus contributing to T2D pathogenesis. Such epigenetic changes can be transmitted to the next generation, contributing to the inheritance of T2D risk. Recent advances in epigenome-wide association studies and epigenetic editing tools present the attractive possibility of identifying epimutations associated with T2D, correcting specific epigenetic alterations, and designing novel epigenetic biomarkers and interventions for T2D.
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