Endocrine Abstracts

Background/objectives: Fibroblast growth factor 21 (FGF21) is a potent hormone known to reduce glycaemia and improve insulin resistance with anti-obesity effects. Although mainly secreted in the liver, adipose tissue is considered an important target for its function. Whilst FGF21 has been shown to be expressed in murine adipose tissue, studies in human adipose tissue are lacking. Therefore our aim was to examine the expression of FGF21, FGF21 receptor-1 (FGFR1), βKlotho (co-factor essential for FGF21 function) in human adipose tissue depots and circulating FGF21 in different metabolic states.

Methods: FGF21, FGFR1, and βKlotho mRNA expression was determined in abdominal subcutaneous (AbdSc) and omental (Om) adipose tissue (n=37: lean, overweight, obese, type 2 diabetes mellitus (T2DM)). Plasma FGF21 (BMI: 31.5±7.9 kg/m²; age: 47.1±10.1 years; n=115) was measured across metabolic states.

Results: βKlotho mRNA expression was significantly increased in AbdSc adipose tissue from obese (11.2 (mean±S.E.M.)0.25ΔCT) subjects compared with lean individuals (12.2±0.3ΔCT; P<0.05). In contrast, βKlotho mRNA expression was significantly reduced in T2DM subjects (13.5±0.3ΔCT) compared with lean (P<0.01), overweight (P<0.001) and obese (P<0.001) individuals. FGFR1 mRNA expression was also reduced in T2DM subjects compared with overweight (T2DM: 12.6±0.2ΔCT vs overweight: 11.8±0.2ΔCT; P<0.01) and obese (obesity: 11.5±0.4ΔCT; P<0.05) individuals. FGF21 was not expressed in any adipose tissue depot or metabolic state. Circulating FGF21 was significantly raised in T2DM subjects compared with lean (P<0.001), overweight (P<0.001) and obese (P<0.05) subjects.

Conclusions/summary: There was no apparent FGF21 expression in human adipose tissue, whilst βKlotho and FGFR1 were expressed and altered by metabolic state. The raised circulating FGF21 in T2DM together with the reduced expression of βKlotho and FGFR1 in AbdSc adipose tissue suggest that although FGF21 acts on adipose tissue, its action may be compromised by metabolic state. Therefore, the reduced βKlotho and FGFR1 adipose tissue expression, despite increased circulating FGF21, could be a reason for the observed ‘FGF21 resistance’ in T2DM.