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