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Why should we consider epigenetics in metabolic disorders?
Complex metabolic disorders including obesity and type 2 diabetes result from intricate interactions between internal genetic makeup and external environment, which is mediated by epigenetic mechanisms. There are compelling reasons to think epigenetic control may have a direct role in the pathogenesis of metabolic dysregulation; 1) Genetic differences can not fully explain many etiological features of metabolic disorders, such as high heritability, high discordance of metabolic disorders in adult monozygotic twins, and the close relationship with lifestyle factors. Therefore, other forms of non-genetic variation, such as epigenetic alterations, should be considered in the etiology. 2) Drugs that affect chromatin remodeling, such as the HDAC inhibitors are known to affect insulin sensitivity in cells, animal models, and human subjects. 3) Collective studies report global and locus-specific epigenetic changes at key metabolic genes often accompanying reduced gene expression in association with various metabolic perturbations. 4) Most convincingly, studies have shown that several mouse genetic models carrying mutations in genes encoding epigenetic modifiers display marked metabolic phenotypes. Despite these notions, the accurate role for the epigenetic modifiers in metabolic regulation largely remains unknown.
Why should we consider epigenetics in metabolic disorders?
Complex metabolic disorders including obesity and type 2 diabetes result from intricate interactions between internal genetic makeup and external environment, which is mediated by epigenetic mechanisms. There are compelling reasons to think epigenetic control may have a direct role in the pathogenesis of metabolic dysregulation; 1) Genetic differences can not fully explain many etiological features of metabolic disorders, such as high heritability, high discordance of metabolic disorders in adult monozygotic twins, and the close relationship with lifestyle factors. Therefore, other forms of non-genetic variation, such as epigenetic alterations, should be considered in the etiology. 2) Drugs that affect chromatin remodeling, such as the HDAC inhibitors are known to affect insulin sensitivity in cells, animal models, and human subjects. 3) Collective studies report global and locus-specific epigenetic changes at key metabolic genes often accompanying reduced gene expression in association with various metabolic perturbations. 4) Most convincingly, studies have shown that several mouse genetic models carrying mutations in genes encoding epigenetic modifiers display marked metabolic phenotypes. Despite these notions, the accurate role for the epigenetic modifiers in metabolic regulation largely remains unknown.
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BIOLOGY-BASELno. 11 (2023): 1450
Hong Sik Yoo, Adrienne Rodriguez,Dongjoo You,Rebecca A. Lee,Michael A. Cockrum, Jack A. Grimes,Jen-Chywan Wang,Sona Kang,Joseph L. Napoli
The Journal of biological chemistry (2021): 100395-100395
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