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.

Background-Adipocyte-fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria. Methods and Results-In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, Pϭ0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (Pϭ0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile, Pϭ0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components. Conclusions-Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.

Objective-Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an important player in atherosclerosis in animal models. However, the clinical relevance of these findings is still unknown. This study aims to examine the relationship between serum A-FABP level and carotid intima-media thickness (IMT), an indicator of atherosclerosis in humans. Methods and Results-The study cohort included 479 Chinese subjects who underwent carotid IMT measurement.Serum A-FABP levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels positively correlated with carotid IMT in both men (rϭ0.211, Pϭ0.001) and women (rϭ0.435, PϽ0.001). In women, but not in men, the presence of plaques was associated with significantly higher serum A-FABP levels (PϽ0.001 versus women without plaques). Stepwise multiple regression analysis showed that serum A-FABP level was independently associated with carotid IMT in women (Pϭ0.034), together with age and hypertension (both PϽ0.001). Conclusions-A-FABP is an independent determinant of carotid atherosclerosis in Chinese women, but not in men.This gender difference may be attributed to the lower serum A-FABP levels in men, and the effect of other risk factors, such as smoking, among our male participants. 2 Earlier animal studies showed that A-FABPnull mice were partially protected from developing hyperinsulinemia, hyperglycemia, and insulin resistance when challenged with dietary and genetic obesity. 3,4 In apolipoprotein E (apoE)-deficient mice, whether on a low-fat or high-fat diet, ablation of the A-FABP gene provided almost complete protection against atherosclerosis, independent of its effects on glucose and lipid metabolism. 5,6 Remarkably, after a high-fat atherogenic Western diet for 1 year, the survival rates of apoE Ϫ/Ϫ mice null for both A-FABP and mal1 were 67% higher than those of apoE Ϫ/Ϫ control mice, primarily because of the increased stability of atherosclerotic plaques. 7 These results suggest that A-FABP is a major mediator of atherosclerotic lesion formation in mice. In humans, A-FABP is expressed in monocytes on PPAR␥ activation, 8 and oxidized LDL has been shown to induce A-FABP expression in human THP-1 macrophage cell lines. 9 Furthermore, a genetic variant associated with increased A-FABP mRNA expression in adipose tissues predicted coronary artery disease in homozygous subjects. 10 These findings suggest that A-FABP may also play a role in the development of atherosclerotic diseases in humans.Although A-FABP was traditionally thought to be an intracellular protein, we have demonstrated that a small portion of A-FABP is released from mature adipocytes into the human blood stream, 11 with the serum concentrations being Ϸ8 to 60 ng/mL. In a cross-sectional study we observed a strong positive association between serum A-FABP levels and parameters of adiposity. In addition, serum A-FABP levels correlated closely with several key features of the metabolic syndrome, an aggregate of cardiometabolic risk factors associated with accelerated atheroscl...

ZAG might be involved in the pathogenesis of obesity-related metabolic disorders in humans and thus warrants further investigation.

OBJECTIVE -To investigate the relationships of serum adipocyte fatty acid-binding protein (A-FABP) and epidermal fatty acid-binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The associations of serum A-FABP and E-FABP with markers of renal function, nephropathy staging, and macrovascular complications were examined in 237 type 2 diabetic patients.RESULTS -Serum A-FABP and E-FABP correlated significantly with serum creatinine, mean albumin excretion rate, and glomerular filtration rate (all P Ͻ 0.001) and were independently associated with diabetic nephropathy staging (P ϭ 0.001 and P Ͻ 0.05, respectively). Circulating levels of both types of FABP were increased (P Ͻ 0.01) in subjects with macrovascular complications. Serum A-FABP was independently associated with macrovascular complications (odds ratio 2.92 [95% CI 1.42-6.01]; P ϭ 0.004).CONCLUSIONS -Serum A-FABP and E-FABP might be novel serum biomarkers for evaluating the progression of nephropathy and its cardiovascular risk in type 2 diabetic patients.

E-FABP is a new circulating biomarker associated with increased cardio-metabolic risk. It may contribute to the development of the MetS and carotid atherosclerosis in humans, independent of the effect of A-FABP.

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In the article listed above, the serum FGF21 data presented in Supplementary Table 1 in the "lean (291.8 ng/L [144.5-512.0])" and "overweight/obese (208.7 ng/L [94.4-325.7])" columns were inversed due to a mistake in typing. It should have been presented as "lean