Abstract
High-fat diets (HFD) are thought to contribute to the development of metabolism-related diseases. The long-term impact of HFD may be mediated by epigenetic mechanisms, and indeed, HFD has been reported to induce DNA methylation changes in white adipose tissue (WAT) near metabolism related genes. However, previous studies were limited to a single WAT depot, a single time-point and primarily examined the pre-pubertal period. To define dynamic DNA methylation patterns specific for WAT depots, we investigated DNA methylation of Pparg2 and Leptin in gonadal adipose tissue (GAT) and subcutaneous adipose tissue (SAT), at baseline and after 6, 12 and 24 weeks of HFD exposure in adult mice. HFD induced hypermethylation of both the Leptin promoter (max. 19.6% at week 24, P = 2.6·10−3) and the Pparg2 promoter in GAT (max. 10.5% at week 12, P = 0.001). The differential methylation was independent of immune cell infiltration upon HFD exposure. In contrast, no differential methylation in the Pparg2 and Leptin promoter was observed in SAT. Leptin and Pparg2 DNA methylation were correlated with gene expression in GAT. Our study shows that prolonged exposure to HFD in adulthood is associated with a gradually increasing DNA methylation level at the Leptin and Pparg2 promoters in a depot-specific manner.
Highlights
Obesity induced by exposure to a high content of saturated fat diet (HFD) is characterized by hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT)
We studied the longitudinal effects of long term High-fat diets (HFD) exposure on DNA methylation of the Leptin and Pparg[2] promoters in two fat depots, gonadal adipose tissue (GAT) and subcutaneous adipose tissue (SAT), in adult mice during the development of obesity
We found consistently accumulating DNA methylation changes in the promoter regions of the Leptin and Pparg[2] genes in GAT over a period of prolonged HFD exposure, whereas DNA methylation remained unaffected in WAT
Summary
Obesity induced by exposure to a high content of saturated fat diet (HFD) is characterized by hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT) It is followed by a chronic state of mild inflammation and changes in adipokine secretion, a phenomenon apparent in metabolically active visceral WAT depots, including gonadal adipose tissue (GAT), rather than subcutaneous adipose tissue (SAT)[1,2]. Pparg[2] is a master regulator of adipogenesis and is involved in adipocyte differentiation and maturation as well as fat storage and glucose metabolism Its activation it thought to have insulin sensitizing effects[6,15,16]. We analysed the impact of immune cell infiltration on DNA methylation and investigated the association between DNA methylation and expression of Leptin and Pparg[2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
