Epigenetics Archives - Episona
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Obesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans
Feb 2016 | Cell Metabolism
Ida Donkin, Soetkin Versteyhe, Lars R. Ingerslev, Kui Qian, Mie Mechta, Loa Nordkap, Brynjulf Mortensen, Emil Vincent R. Appel, Niels Jørgensen, Viggo B. Kristiansen, Torben Hansen, Christopher T. Workman, Juleen R. Zierath, Romain Barrès
Obesity is a heritable disorder, with children of obese fathers at higher risk of developing obesity. Environmental factors epigenetically influence somatic tissues, but the contribution of these factors to the establishment of epigenetic patterns in human gametes is unknown. Here, we hypothesized that weight loss remodels the epigenetic signature of spermatozoa in human obesity. <!--more-->Comprehensive profiling of the epigenome of sperm from lean and obese men showed similar histone positioning, but small non-coding RNA expression and DNA methylation patterns were markedly different. In a separate cohort of morbidly obese men, surgery-induced weight loss was associated with a dramatic remodeling of sperm DNA methylation, notably at genetic locations implicated in the central control of appetite. Our data provide evidence that the epigenome of human spermatozoa dynamically changes under environmental pressure and offers insight into how obesity may propagate metabolic dysfunction to the next generation.
Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring
Feb 2016 | Cell Metabolism
Ling Wu, Yan Lu, Yang Jiao, Bin Liu, Shangang Li, Yao Li, Fengying Xing, Dongbao Chen, Xing Liu, Jiejie Zhao, Xuelian Xiong, Yanyun Gu, Jieli Lu, Xuejin Chen, and Xiaoying Li
Both epidemiologic and experimental animal studies demonstrate that chronic psychological stress exerts adverse effects on the initiation and/or progression of many diseases. However, intergenerational effects of this environmental information remains poorly understood. Here, using a C57BL/6 mouse model of restraint stress, we show that offspring of stressed fathers exhibit hyperglycemia due to enhanced hepatic gluconeogenesis and elevated expression of PEPCK. <!--more-->Mechanistically, we identify an epigenetic alteration at the promoter region of the Sfmbt2 gene, a maternally imprinted polycomb gene, leading to a downregulation of intronic microRNA-466b-3p, which post-transcriptionally inhibits PEPCK expression. Importantly, hyperglycemia in F1 mice is reversed by RU486 treatment in fathers, and dexamethasone administration in F0 mice phenocopies the roles of restraint stress. Thus, we provide evidence showing the effects of paternal psychological stress on the regulation of glucose metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers.