| Objective Netrin-1, a diffusible axon-guiding molecule, is playing an important role in the non-nervous system. Recently, several lines of findings have suggested that Netrin-1 takes part in pathogenesis of obesity. However, knowledge regarding the relationship between Netrin-1 and obesity in humans is limited. This study measured for the first time serum Netrin-1 levels between normal weight and overweight/obesity, and explored the correlations between its serum levels and various metabolic parameters such as BMI, waist circumference and waist-to-hip ratio, then to further explore the value of Netrin-1 to obesity.Methods A total of 150 subjects were divided into normal weight group(n = 76) and overweight/obesity group(n = 74) based on a body mass index(BMI) ≥ 25 kg/m2 according to the World Health Organization-Western Pacific Region diagnostic criteria(2000). All subjects were also divided into three subgroups, Tertile1, Tertile2 and Tertile3(n = 50), according to the levels of serum Netrin-1. A standard, scripted questionnaire, anthropometric parameters were conducted by trained study personnel. Human body parameters such as blood pressure, height, body weight, waist circumference(WC) and hip circumference were measured by professionals, then calculate body mass index(BMI), waist hip ratio(WHR). Hb A1 c, fasting plasma glucose(FPG), fasting insulin(FINS), 2h postprandial plasma glucose(2h PG), 2h postprandial serum insulin(2h INS) and lipids and other biochemical parameters were also detected. Serum netrin-1 levels were determined using a commercially available human enzyme-linked immunosorbent assays(ELISA) kit according to the manufacturer’s instructions. The estimate of insulin resistance was used by homeostasis model assessment index(HOMA-IR).Results(1) Compared with the normal weight group, BMI, WC, WHR, blood pressure, FINS, 2h PG, triglyceride and HOMA-IR in overweight/obesity group were significantly increased(P < 0.05 or P < 0.01).(2) Serum Netrin-1 levels were significantly lower in overweight/obesity patients than in normal weight subjects(P < 0.01).(3) According to the levels of serum Netrin-1, all subjects were divided into three groups, Tertilel, Tertile2, Tertile3. Compared with the Tertilel group, BMI and WC in Tertile2 and Tertile3 group were significantly decreased. The age was higher in Tertile3 group than in Tertilel group(P < 0.05 or P < 0.01).(4) Pearson correlation analysis showed that serum netrin-1 correlated positively with age in the total participants(r = 0.181, P < 0.05), while negatively correlated with BMI and WC(r =-0.320、-0.280, P < 0.01). After adjustment for age, BMI and WC remained significantly correlated with serum Netrin-1 levels(P < 0.01).(5) Multivariate regression models were fit for Netrin-1 as a dependent variable, age, BMI, WC, Hb A1 c, FPG, 2h PG, FINS, 2h INS and HOMA-IR as independent variables to demonstrate the relative contribution to the outcome ones. The results showed that age(β = 0.161, P = 0.038) and BMI(β =-0.310, P = 0.000) were independently related factors influencing serum Netrin-1 level(R2 = 0.129, P = 0.000).(6) Binary logistic regression analyses showed that circulating Netrin-1 was significantly associated with overweight/obesity even adjustment for sex, age, WC, blood pressure, Hb A1 c, FPG, 2h PG, FINS, 2h INS, HOMA-IR and lipid profile. Netrin-1 was a protective factor of overweight/obesity, while WC, TG, TC were the risk ones.Conclusion(1) Serum Netrin-1 levels in overweight/obesity patients were significantly lower than in normal weight subjects, associated with age positively and BMI and WC negatively.(2) The degree of overweight/obesity was significantly improved when levels of serum Netrin-1 were increased.(3) High levels of serum Netrin-1 were the protective factor of overweight/obesity, which may play an important role in the pathogenesis of overweight/obesity. |
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