Dietary induction of obesity and insulin resistance is associated with changes in Fgf21 DNA methylation in liver of mice

• DOI: 10.1016/j.jnutbio.2021.108907
• Publication Date: 2021-11-18T16:37:50Z
• Authors: Cathleen Geißler; Christin Krause; Anne-Marie Neumann; Jan H. Britsemmer; Natalie Taege; Martina Grohs; Meike Kaehler; Ingolf Cascorbi; Alfor G. Lewis; Randy J. Seeley; Henrik Oster; Henriette Kirchner
• Keywords: FGF21; Steatosis

DNA methylation is dynamically regulated in metabolic diseases, but it remains unclear whether the changes are causal or consequential. Therefore, we used a longitudinal approach to refine onset of and at high temporal resolution. Male C57BL/6N mice were fed with 60 % high-fat diet (HFD) for up 12 weeks metabolically characterized weekly. Liver was collected after 1, 2, 4, 5, 6, 7, 8, hepatic gene expression analyzed. A subset obese underwent vertical sleeve gastrectomy (VSG) metformin treatment livers studied. Distinct patterns developed upon feeding HFD, genes from fatty acid metabolism pathway being predominantly altered. When comparing data methylation, particular Fgf21 decreased before increased changes. Neither weight loss induced by VSG nor improved glucose tolerance could revert expression. Our emphasize dynamic induction stimuli. Reduced established massive overexpression Fgf21, which likely an adaptive effort liver maintain homeostasis despite developing insulin resistance steatosis. resisted reversion intervention strategies, illustrating long-term effects unhealthy lifestyle. provide roadmap development resistance, comprehensively linking data.