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Published online February 5, 2008
Diabetes 57:1246-1253, 2008
DOI: 10.2337/db07-1476
© 2008 by the American Diabetes Association
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Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans

Xinmei Zhang1,2, Dennis C.Y. Yeung1,2, Michal Karpisek3, David Stejskal4, Zhi-Guang Zhou8, Feng Liu5,6, Rachel L.C. Wong1,2, Wing-Sun Chow1,2, Annette W.K. Tso1,2, Karen S.L. Lam1,2, and Aimin Xu1,2,7

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

Corresponding author: Aimin Xu or Karen S.L. Lam, Department of Medicine, University of Hong Kong, L8-43, New Laboratory Block, 21 Sassoon Road, Hong Kong, China. E-mail: amxu{at}hkucc.hku.hk and ksllam{at}hku.hk

Key Words: A-FABP, adipocyte–fatty acid–binding protein • ELISA, enzyme-linked immunosorbent assay • FGF, fibroblast growth factor • HOMA-IR, homeostasis model assessment index–insulin resistance • IL, interleukin • NCEP, National Cholesterol Education Program • NGT, normal glucose tolerance • OGTT, oral glucose tolerance test • PPAR, peroxisome proliferator–activated receptor • QUICKI, quantitative insulin sensitivity check index • TNF-{alpha}, tumor necrosis factor-{alpha}

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 cardiometabolic 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 between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. 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 compared with that in 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.


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Copyright © 2008 by the American Diabetes Association.