Maternal High-Fat Diet Disturbs the DNA Methylation Profile in the Brown Adipose Tissue of Offspring Mice

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.

Differentially methylated regions identified in bovine embryos are not observed in adulthood

“…Several studies have confirmed the effect of different maternal diets on the offspring in humans (Roseboom et al, 2006), mice (Guo et al, 2018;Mao et al, 2018;Xie et al, 2018), rats (Carlin et al, 2019;Pedrana et al, 2020), and bovines (Devos et al, 2021;Liu et al, 2021;Noya et al, 2021). Moreover, studies reported that the maternal diet during gestation affects the DNA methylation pattern in the placenta and offspring of mice (Ge et al, 2014;Mahajan et al, 2019;Zhang et al, 2021a), cattle (Liu et al, 2021), and humans (Daniels et al, 2020;Kupers et al, 2022). Interestingly, a study showed that the exposure of IVP embryos to choline in the culture medium alters the DNA methylation profile in the offspring muscle (Estrada-Cortes et al, 2021).…”

The Multi-Omics Analyses of ACSL1 Reveal Its Translational Significance as a Tumor Microenvironmental and Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

“…Wang et al suggested that ACSL1 down-regulation was caused by copy number deletion in breast cancer (21). Nevertheless, in the brown adipose tissue, DNA hypermethylation led to the decreased expression of ACSL1 (22). The role of dysregulation of the epigenome, like DNA/RNA methylation and histone modi cation, in driving cancer evolution and advancement, has been increasingly understood and highlighted.…”

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity

“…Further, the offspring of obese mothers demonstrate elevated plasma triglyceride and reduced plasma high-density lipoprotein cholesterol levels, with abnormal fatty acid composition in the aorta [ 74 ]. The brown adipose tissue metabolism in 16-week-old male offspring of obese dams has also been shown to have a disordered function, with the increased activation of DNA methylation of the genes involved in fatty acid oxidation, thermogenesis and impaired brown adipose tissue structure [ 75 ]. Rodent models have clearly demonstrated the detrimental effect of maternal obesity on transgenerational cardiovascular risk.…”