Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High-Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation.

Autor:	Kusuyama J; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.; Frontier Research Institute for Interdisciplinary Sciences, Tohoku University, Sendai, Japan.; Division of Biomedical Engineering for Health and Welfare, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan., Makarewicz NS; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Albertson BG; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Alves-Wagner AB; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Conlin RH; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Prince NB; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Alves CRR; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Ramachandran K; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Kozuka C; YCI Laboratory for Metabolic Epigenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan., Xiudong Y; Graduate School of Biomedical Sciences, University of Texas at Houston, Houston, TX., Xia Y; Graduate School of Biomedical Sciences, University of Texas at Houston, Houston, TX., Hirshman MF; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA., Hatta T; Department of Anatomy, Kanazawa Medical University, Kanazawa, Japan., Nagatomi R; Division of Biomedical Engineering for Health and Welfare, Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.; Department of Medicine and Science in Sports and Exercise, Tohoku University School of Medicine, Sendai, Japan., Nozik ES; Cardiovascular Pulmonary Research Laboratories and Pediatric Critical Care, Department of Pediatrics, University of Colorado Anschutz Medical Center, Aurora, CO., Goodyear LJ; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2022 Jun 01; Vol. 71 (6), pp. 1170-1181.
DOI:	10.2337/db21-0706
Abstrakt:	Preclinical studies reveal maternal exercise as a promising intervention to reduce the transmission of multigenerational metabolic dysfunction caused by maternal obesity. The benefits of maternal exercise on offspring health may arise from multiple factors and have recently been shown to involve DNA demethylation of critical hepatic genes leading to enhanced glucose metabolism in offspring. Histone modification is another epigenetic regulator, yet the effects of maternal obesity and exercise on histone methylation in offspring are not known. Here, we find that maternal high-fat diet (HFD; 60% kcal from fat) induced dysregulation of offspring liver glucose metabolism in C57BL/6 mice through a mechanism involving increased reactive oxygen species, WD repeat-containing 82 (WDR82) carbonylation, and inactivation of histone H3 lysine 4 (H3K4) methyltransferase leading to decreased H3K4me3 at the promoters of glucose metabolic genes. Remarkably, the entire signal was restored if the HFD-fed dams had exercised during pregnancy. WDR82 overexpression in hepatoblasts mimicked the effects of maternal exercise on H3K4me3 levels. Placental superoxide dismutase 3 (SOD3), but not antioxidant treatment with N-acetylcysteine was necessary for the regulation of H3K4me3, gene expression, and glucose metabolism. Maternal exercise regulates a multicomponent epigenetic system in the fetal liver resulting in the transmission of the benefits of exercise to offspring. (© 2022 by the American Diabetes Association.)
Databáze:	MEDLINE
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