AUTHOR=Zhang Qian , Xiao Xinhua , Zheng Jia , Li Ming , Yu Miao , Ping Fan , Wang Tong , Wang Xiaojing TITLE=Maternal High-Fat Diet Disturbs the DNA Methylation Profile in the Brown Adipose Tissue of Offspring Mice JOURNAL=Frontiers in Endocrinology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2021.705827 DOI=10.3389/fendo.2021.705827 ISSN=1664-2392 ABSTRACT=

The prevalence of obesity has become a threatening global public health issue. The consequence of obesity is abnormal energy metabolism. Unlike white adipose tissue (WAT), brown adipose tissue (BAT) has a unique role in nonshivering thermogenesis. Lipids and glucose are consumed to maintain energy and metabolic homeostasis in BAT. Recently, accumulating evidence has indicated that exposure to excess maternal energy intake affects energy metabolism in offspring throughout their life. However, whether excess intrauterine energy intake influences BAT metabolism in adulthood is not clear. In this study, mouse dams were exposed to excess energy intake by feeding a high-fat diet (HFD) before and during pregnancy and lactation. The histology of BAT was assessed by hematoxylin and eosin staining. The genome-wide methylation profile of BAT was determined by a DNA methylation array, and specific site DNA methylation was quantitatively analyzed by methylated DNA immunoprecipitation (MeDIP) qPCR. We found that intrauterine exposure to a high-energy diet resulted in blood lipid panel disorders and impaired the BAT structure. Higher methylation levels of genes involved in thermogenesis and fatty acid oxidation (FAO) in BAT, such as Acaa2, Acsl1, and Cox7a1, were found in 16-week-old offspring from mothers fed with HFD. Furthermore, the expression of Acaa2, Acsl1, and Cox7a1 was down-regulated by intrauterine exposure to excess energy intake. In summary, our results reveal that excess maternal energy leads to a long-term disorder of BAT in offspring that involves the activation of DNA methylation of BAT-specific genes involved in fatty acid oxidation and thermogenesis.