PRJNA484788
Mus musculus isolate:Liver Transcriptome or Gene expression
Fibroblast growth factor 21 (FGF) is an endocrine hormone that regulates glucose, lipid, and energy homeostasis. We show that mice with a mutation in the Yip1 domain family, member 6 gene (Yipf6KLZ/Y) are resistant to high-fat diet (HFD)-induced features of the metabolic syndrome and have increased lipolysis, energy expenditure, and thermogenesis with an increase in core body temperature. Yipf6KLZ/Y mice on a HFD have higher plasma levels of Fibroblast growth factor 21 (FGF21) than mice that do not carry this mutation (controls), and hepatocytes from Yipf6KLZ/Y mice secrete more FGF21 than hepatocytes from wild-type mice. Yipf6KLZ/Y mice with hepatocyte-specific deletion of FGF21 were no longer protected from diet-induced obesity. Levels of YIPF6 protein in human liver correlate with hepatic steatosis, and correlate inversely with levels of FGF21 in serum from patients with non-alcoholic fatty liver disease (NAFLD). YIPF6 is therefore a newly identified regulator of FGF21 secretion during development of obesity and could be a target for treatment of obesity and NAFLD.