Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans

Abstract

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 developedimmunoassay 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.

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

“…On the contrary, there is no strict correlation between FGF21 levels and fat mass in obese patients. In particular, the association of serum FGF21 levels with BMI and fat percentage is weaker than other adipokines predominantly produced from adipose tissue, such as leptin [30] .…”

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

“…In particular, Camporez et al showed that these improvements were associated with reduced hepatocellular triglyceride and diacylglycerol contents, decreased activation of PKCε in the liver, as well as improved insulin signaling (Camporez et al, 2013b). Interestingly, in humans, FGF21 plasma levels increase in situations of insulin resistance such as obesity, type 2 diabetes and NAFLD (Chavez et al, 2009;Dushay et al, 2010;Li et al, 2010;Zhang et al, 2008). This increase in FGF21 plasma levels may reflect a state of FGF21 resistance.…”

Relationship of fibroblast growth factor 21 with baseline and new on-study microvascular disease in the Fenofibrate Intervention and Event Lowering in Diabetes study

“…FGF21 regulates peroxisome proliferator-activated receptor-γ (PPAR-γ ) and the glucose-l ow ering acti vi ty of thiazolidinediones [3,4]. Despite these beneficial effects of FGF21 in glucose metabolism in animal studies, circulating FGF21 levels are often elevated in obesity, dyslipidaemia, insulin resistance, type 2 diabetes and coronary artery disease [2,[5][6][7]. The elevation in FGF21 levels may be a compensatory response to underlying metabolic stress or may be due to impaired FGF21 signalling leading to FGF21 resistance [8].…”