Title: YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity.

Accession Number: SRP156495

Link to Dataset: https://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP156495

Repository: Sequence Read Archive (SRA)

Data Type(s): Nucleotide Sequence

Experiment Type(s): Transcriptome analysis

Organism(s): Mus musculus

Summary: 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.

Publication(s) associated with this dataset:

• Wang L, Mazagova M, Pan C, Yang S, Brandl KL, Liu J, Reilly SM, Wang Y, Miao Z, Loomba R, Lu N, Guo Q, Liu J, Yu RT, Downes M, Evans RM, Brenner DA, Saltiel AR, Beutler B, Schnabl B. 2019. YIPF6 controls sorting of FGF21 into COPII vesicles and promotes obesity. Proc Natl Acad Sci U S A 116:15184-15193. doi:10.1073/pnas.1904360116 PMID:31289229 PMCID:PMC6660779