Changes in Fibroblast Growth Factor 21 with Modest Weight Loss

Abstract

Fibroblast growth factor 21 (FGF21) - one of several atypical fibroblast growth factors with endocrine hormone functions - has been shown to stimulate insulin-mediated glucose uptake in adipocytes and to increase fat utilization and energy expenditure. FGF21 concentrations appear to be greater in obese and insulin resistant individuals; however, information on the FGF21 response to modest weight loss is scant. PURPOSE: The objectives of this investigation were to characterize the effects of modest weight loss on circulating concentrations of FGF21 and to determine relationships between FGF21 and changes in body composition and insulin sensitivity in obese men. METHODS: Nine obese men (age = 41.5 +/- 7.1; weight = 101.7 +/- 21.0 kg; BMI = 32.8 +/- 3.6 kg/m2; body fat = 35 +/- 4%) were assigned to exercise and dietary restriction in order to reach a targeted weight loss of 8 to 10% of initial body weight over a 6 to 10-month period. Blood samples were analyzed for glucose, insulin and clinical markers of insulin sensitivity; FGF21, non-esterified fatty acids, adiponectin, interleukin-6 and tumor necrosis factor-alpha concentrations; and myeloperoxidase activity (MPOa) at regular weight loss intervals (2-4%, 4-6%, 6-8% and target weight loss). RESULTS: Body fat decreased by 4% (p < 0.0001) and lean mass decreased by 3% (p < 0.0001) with the targeted weight loss. Markers of insulin sensitivity (HOMA = -28.6%; glucose/insulin ratio = +17.9%) were improved with as little as 4-6% weight-loss (p < 0.0006). FGF21 was significantly reduced with 2-4% weight loss and decreased by 57.3% with target weight loss (p = 0.0051). Changes in total lean mass and fat mass were not correlated, but together accounted for 36% of the variation in FGF21 (p < 0.0001). The improved insulin sensitivity with weight loss was not correlated with changes in FGF21 or to changes in lean and fat mass. CONCLUSIONS: Modest weight loss resulted in improved insulin sensitivity and a decrease in FGF21 concentrations. Measurable changes in lean and fat mass, FGF21, and insulin sensitivity do not appear to occur simultaneously with weight loss. Funded by an Alabama Agriculture Experiment Station Foundation Grant