A PPARγ-FGF1 axis is required for adaptive adipose remodeling

We identify fibroblast growth factor 1 (FGF1) as a critical transducer in adipose tissue remodeling and link its regulation to peroxisome proliferator activated-receptor γ (PPARγ), the adipocyte master regulator and target of the thiazolidinedione (TZD) class of insulin sensitizing drugs. We show that FGF1 is highly induced in adipose tissue in response to high-fat diet (HFD) and that mice lacking FGF1 develop an aggressive diabetic phenotype coupled to aberrant adipose expansion when challenged with HFD. Mechanistically, we show that transcription of FGF1 is directly regulated by an adipocyte-selective proximal PPAR response element, and that this PPARγ-FGF1 axis is evolutionarily conserved in mammals. This work describes the first phenotype of the FGF1 knockout mouse and establishes FGF1 as a new member of the NR-FGF axis critical for maintaining metabolic homeostasis and insulin sensitization. Total RNA was obtained from epidydimal white adipose tissue (eWAT) and livers from 6 month old wild-type and FGF1-/- mice after 16 weeks on normal chow or high-fat diets.