Serum Leptin as a Mediator of the Influence of Insulin Resistance on Hepatic Steatosis in Youths with Excess Adiposity

Background and aims: The relationship between insulin resistance (IR) and hepatic steatosis (fatty liver) is well known; however, the extent to which the satiety hormone leptin acts as a confounder or mediator in this relationship is uncertain. We examined whether the association between IR and hepatic steatosis is mediated by leptin in Colombian adolescents with excess adiposity. Methods and results: A total of 122 adolescents (mean age: 13.4 years; 68% girls) participated in the study. We assessed body composition, hepatic steatosis (as defined by the controlled attenuation parameter [CAP]), cardiometabolic risk factors (body mass index, waist circumference, body composition), biochemical variables (leptin, insulin, glucose, lipid profile, cardiometabolic Z-score, transaminases, etc.), and physical fitness (cardiorespiratory fitness and grip strength). Partial correlation, regression, and mediation analyses were conducted using the Barron and Kenny framework. Results: Ninety-two youths (75.4%) had IR. Mediation analysis revealed a positive relationship between Homeostasis Model Assessment-IR (HOMA-IR) and CAP (βdir = 3.414, 95% confidence interval [CI]: 1.012 to 5.816, p < 0.001), which was attenuated when leptin was included in the model, thus indicating that leptin mediates this relationship (βind = 1.074, 95% CI: 0.349 to 2.686, p < 0.001). The percentage of the total effect mediated by leptin was 21%. Regarding sex, the mediation effect of leptin remains significant among boys (βind = 0.962, 95% CI: 0.009 to 2.615, p < 0.001), but not in girls (βind = 0.991, 95% CI: 1.263 to 5.483, p = 0.477). Conclusions: The findings are clinically relevant to consider leptin levels as a surrogate marker of insulin sensitivity when assessing youths with excess adiposity and/or suspected Nonalcoholic hepatic steatosis or nonalcoholic fatty liver disease (NAFLD). © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University