OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a metabolic factor involved in glucose and lipid metabolism. However, little is known about the physiological role of FGF21 during a dietary challenge in humans.

RESEARCH DESIGN AND METHODS: Twenty healthy low birth weight (LBW) with known risk of type 2 diabetes and 26 control (normal birth weight (NBW)) young men were subjected to 5 days of high-fat (HF) overfeeding (+50%). Basal and clamp insulin-stimulated serum FGF21 levels were examined before and after the diet, and FGF21 mRNA expression was measured in muscle and fat biopsies respectively.

RESULTS: Five days of HF overfeeding diet significantly (P<0.001) increased fasting serum FGF21 levels in both the groups (P<0.001). Furthermore, insulin infusion additionally increased serum FGF21 levels to a similar extent in both the groups. Basal mRNA expression of FGF21 in muscle was near the detection limit and not present in fat in both the groups before and after the dietary challenge. However, insulin significantly (P<0.001) increased FGF21 mRNA in both muscle and fat in both the groups during both diets.

CONCLUSION: Short-term HF overfeeding markedly increased serum FGF21 levels in healthy young men with and without LBW but failed to increase muscle or fat FGF21 mRNA levels. This suggests that the liver may be responsible for the rise of serum FGF21 levels during overfeeding. In contrast, the increase in serum FGF21 levels during insulin infusion may arise from increased transcription in muscle and fat. We speculate that increased serum FGF21 levels during HF overfeeding may be a compensatory response to increase fatty acid oxidation and energy expenditure.