The fibroblast growth factor (FGF) family is best characterized for its role in developmental processes and differentiation of various cell types. In a screen to identify factors that respond to metabolic cues, Jonker et al. found that the abundance of FGF1A was increased in visceral white adipose tissue in mice on a high-fat diet. Fgf1–/– mice did not show metabolic changes when fed a standard diet, consistent with previous reports. However, Fgf1–/– mice on a high-fat diet exhibited signs of a diabetic phenotype, including increased glucose and insulin serum concentrations, insulin resistance, and signs of macrophage infiltration. However, on the high-fat diet, both the knockout and the wild-type mice gained the same amount of weight. The visceral white adipose tissue of Fgf1–/– mice showed decreased vascular density and decreased expression of the gene encoding elastase 1, a tissue remodeling factor. White adipose tissue can increase or decrease in mass, and the authors assessed the role of FGF1A in the reduction in adipose tissue mass by switching mice on a high-fat diet to a standard diet. In this feeding paradigm, fragments of necrotic fat tissue were detected in the peritoneal cavity of Fgf1–/– mice but not wild-type mice. In response to increased nutrient availability, the nuclear receptor PPARγ (peroxisome proliferator–activated receptor γ) transcriptionally activates genes that promote adipogenesis and glucose uptake. The promoter region of the FGF1A transcript contained a PPAR response element, and chromatin immunoprecipitations confirmed that PPARγ bound to the PPAR response element in 3T3-L1 adipocytes. Mice treated with the PPARγ ligand rosiglitazone showed increased Fgf1a transcript abundance in visceral white adipose tissue when fed but not when fasted. Thus, FGF1A is involved in changes in white adipose tissue mass in response to nutrient availability.
J. W. Jonker, J. M. Suh, A. R. Atkins, M. Ahmadian, P. Li, J. Whyte, M. He, H. Juguilon, Y.-Q. Yin, C. T. Phillips, R. T. Yu, J. M. Olefsky, R. R. Henry, M. Downes, R. M. Evans, A PPARγ-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature 485, 391–394 (2012). [PubMed]