The Association Of Serum Adipocyte Fatty Acid Binding Protein With Adolescent Obesity

BACKGROUNDObesity, characterized by excess accumulation of adipose tissue, is the most common risk factor for metabolic syndrome, a cluster of abnormalities including dyslipidemia, insulin resistance, hypertension, and atherosclerosis. Although the molecular pathways that link obesity with such a wide spectrum of metabolic and cardiovascular defects are poorly understood, recent studies indicated a central role of adipose tissue in the development of this syndrome. Accumulating evidence suggests that adipose tissue is not simply an inert energy storage depot but also functions as a major endocrine organ, producing and releasing a variety of bioactive adipokines into the bloodstream. These adipose tissue–derived bioactive molecules, through their local and systemic actions, are postulated to regulate energy metabolism, insulin sensitivity, inflammation, and vascular responses.Adipocyte-specific fatty acid–binding protein (A-FABP) belongs to the fatty acid–binding proteins accounting for approximately 6% of total cellular proteins. This protein may be an important regulator of systemic insulin sensitivity and lipid and glucose metabolism. Mice deficient in A-FABP are protected from development of hyperinsulinemia, hyperglycemia, and insulin resistance in the context of both dietary and genetic obesity. Adipocytes obtained from A-FABP–null mice had markedly reduced efficiency of lipolysis in vivo and in vitro and exhibited a 2- to 3-fold decrease in fatty acid release, suggesting that A-FABP mediates efflux of fatty acids in normal physiology. Furthermore, the acute insulin secretory response toβ-adrenergic stimulation was profoundly suppressed in A-FABP(?/?) mice compared with their wild-type littermates, suggesting that this protein modulates systemic insulin sensitivity through its actions on other distal target tissues. Recently, Furuhashi et al demonstrated that orally available small molecule inhibitors of fatty acid–binding protein were effective in treating diabetes and atherosclerosis in mice.Adipocyte fatty acid–binding protein is present in adipocytes and macrophages, which bear striking similarities to adipocytes in biology and function. The expression of A-FABP can be suppressed by cholesterollowering statin drugs. Adipocyte fatty acid– binding protein modulates inflammatory cytokine production and cholesterolester accumulation. In apolipoprotein E deficient mice, ablation of the A-FABP gene conferred remarkable protection against atherosclerosis. Taken together, these animal studies suggest that A-FABP, by integrating metabolic and inflammatory pathways, may be a link between various components of metabolic syndrome, systemic chronic inflammation, and obesity. Nevertheless, the clinical relevance of these findings remains to be confirmed in humans.One study in obese adults postulated a strong relationship between weight status, markers of the metabolic syndrome, and A-FABP. However, because this study was crosssectional, these data have to be interpreted with caution while longitudinal data are required but still missing. Moreover, because atherosclerosis and the feature of metabolic syndrome begin in childhood, studies on population and individual differences in the early onset and progression of possible initiating risk factors through childhood are important. One further advantage of examining children is that no potential confusion exists with coronary disease or active tobacco smoking. However, to our best knowledge, no studies concerning AFABP have yet been performed in childhood. Positively control the hyperglycaemia is expected to control the development of disease, prevent further expand of infarction circumscription, reduce brain damage, and reduce mortality.OBJECTIVETherefore, we designed the present study to investigate whether the circulating concentrations of A-FABP correlate with adiposity and components of the metabolic syndrome in adolescents. To demonstrate whether A-FABP concentrations are already altered in obese children,to analyse the association of A-FABP levels with abdominal obesity and to evaluate A-FABP levels as markers of abdominal obesity in adolescent.PATIENTS AND METHODS1. Subjects:We recruited randomly a total of 174 high-school (101 male and 73 female;age range,17-21 years ) students from Yangpu Distric,Shanghai. Adolescents with endocrine disorders, cardiovascular, gastrointestinal or renal disorders, or syndromal obesity , or acute or chronic inflammation were all excluded from the study were excluded from the study. All participants were nonsmokers without any regular medication.They were divided into 3 groups by BMI and waist circumference according to the guidelines of the World Health Organization,including groupe A,normal weight;groupe B,non-abdominal obesity;groupe C,abdominal obesity. The study protocol was approved by the Ethics Committee of Changhai Hospital, Second Military Medical University in Shanghai, and informed consent was obtained from the children or from their legal guardians.2. Methods: Anthropometric measurements (height, weight, waist circumference, thigh circumference, BMI, and systolic and diastolic blood pressures) were performed as reported previously. The methods for measurement of biochemical variables, including fasting insulin and glucose concentrations,uric acid, lipid profiles (total cholesterol, LDL-cholesterol, HDL-cholesterol, and total serum triglycerides) were enzymic methods. Insulin was determined by radioimmunoassay. The homeostasis model assessment (HOMA) of insulin resistance, a simple assessment of insulin sensitivity, was calculated with the following formula: fasting plasma glucose (mmol/L)×fasting insulin (mIU/L)/22.5.Serum A-FABP concentrations were assessed by a high-specific enzyme-linked immunoassay (human A-FABP ELISA; BioVendor Laboratory Medicine Inc.). The sensitivity was 0.1μg/L. Intra- and interassay CVs were 3.9%-6.6% and 2.6%-5.1%, respectively.3. Statistical analysis: All statistical calculations were performed with the SAS 9.1 statistical analysis system (SAS Inc.). A comparison of values between normal-weight , overweight and obese individuals was performed using one-way analysis of variance (ANOVA) or Kruskal-Wallis H Test . Comparison of values in all groups classified by WC,TC,TG,HDL-C,LDL-C was maded by T-test. The Pearson correlation coefficient was used to establish the association between A-FABP concentrations and various anthropometric and biochemical measures. The multiple linear regression is further used for analysis the relationship between these factors and serum A-FABP concentrations among these groups. All data are expressed as the mean±SD, and P values <0.05 were considered statistically significant RESULTS1. Clinical characteristics of subjects:Among the obese subjects,they had significantly higher waist circumference, waist to hip ratio, waist to thigh ratio, the HOMA index, levels of the blood presure(SBP and DBP), fasting insulin, 2-h postprandial glucose, Ua, TG and lower HDL-c (p< 0.01) compared with nonobses adolescents. The obese and overweight subjects have higher levels of LDL-c than the normal weight adolescents(p<0.05), while no difference between the obese and overweight ones. Furthermore, we found no difference in levels of total cholesterol, fasting glucose among the three groupes.2. serum a-fabp concentrations is increased in overweight/obese adolescents:We next measured the serum concentrations of AFABP in 41normal weight , 86 overweight and 47 obese individuals. serum concentrations of A-FABP were strikingly higher(P<0.01) in obese individals compared to the overweight group and the normal weight group. These results were consistent for both genders. Notably, serum A-FABP concentrations in male were lower than in female among obese individuals (P <0.05). but not in normal-weight or overweight individuals. We observed a strong positive correlation between serum A-FABP concentrations and BMI in both men (r = 0.54; P <0.0001) and women (r =0.651; P <0.001).3. serum a-fabp concentrations are closely related to the components of metabolic syndrome. After adjustment for sex , serum concentrations of A-FABP were positively correlated with BMI, waist circumference,waist-to-hip ratio, waist to thigh ratio, systolic and diastolic blood pressure; fasting serum concentrations of insulin, Ua, triglycerides, total cholesterol and LDLcholesterol; 2-h postprandial glucose; and the HOMA Index(p<0.05). The serum concentrations of A-FABP increased significantly as the concentrations of components of metabolic syndrome increased. A linear and significant trend was observed. While no significant coorelation is observed between A-FABP and fasting glucose , HDLcholesterol.CONCLUSION1. Taken together, these studies suggest that A-FABP, by integrating metabolic and inflammatory pathways, may be a promising key link between various components of metabolic syndrome, systemic chronic inflammation, and obesity. This highlights the clinical significance of A-FABP.2. Increase of serum A-FABP is strongly related to the disorders of glycose and lipid metabolism in adolescent abdominal obesity , measurement of serum A-FABP concentrations might be useful for diagnosis and prevention of MS and abdominal obesity in adolescent.