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Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans

¹Department of Medicine, and
²Research Centre of Heart, Brain, Hormone and Healthy Aging,
³Department of Pharmacology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China
⁴Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic
⁵Department of Laboratory Medicine, Sternberk Hospital, Czech Republic
⁶Department of Biochemistry and
⁷Pharmacology, UTHSTCSA, San Antonio, TX78229
⁸ Diabetes Center, Institute of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University, Changsha, China

Objective: Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardio-metabolic parameters in humans.

Research Design And Methods: A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR.

RESULTS: Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin and triglycerides, but negatively with HDL-cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association betweenserum FGF21 and the metabolic syndrome (MetS). Furthermore, the increased risk of the MetS associated with high serum FGF21 was over and above the effects of individual components of the MetS. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue comparing with their lean littermates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans.

CONCLUSIONS: FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The "paradoxical" increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation.

Correspondence: ksllam{at}hku.hk

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