Circulating THBS1: A Risk Factor for Nonalcoholic Fatty Liver Disease in Obese Children

Abstract

<b><i>Introduction:</i></b> Thrombospondin 1 (THBS1) is a highly expressed adipokine in adults with obesity. In the present study, we aimed to investigate the clinical significance of THBS1in children with obesity and nonalcoholic fatty liver disease (NAFLD) and determine the effect of metformin on THBS1 expression in dietary-induced obese (DIO) mice. <b><i>Methods:</i></b> A cross-sectional study was conducted among 78 obese children and 35 nonobese children. Anthropometric parameters, clinical data, and circulating THBS1 levels were measured. The expression of THBS1 was detected in the serum and liver tissue from diet-induced obese mice (C57BL/6) with or without metformin treatment. <b><i>Results:</i></b> Higher THBS1 levels were observed in children with NAFLD and higher SDS-BMI. Individuals in the higher THBS1 quartile had a higher prevalence of hypo-high-density lipoprotein cholesterol (HDL-C). Logistic regression analysis showed a significant correlation between THBS1 and NAFLD, as well as between hip circumference and leptin levels. Receiver-operating characteristic (ROC) analysis revealed that THBS1 was a more sensitive predictor of NAFLD than leptin. Additionally, metformin ameliorated hepatic steatosis and decreased hepatic THBS1 expression in high-fat diet (HFD)-fed mice. <b><i>Conclusions:</i></b> Circulating THBS1 level may be a risk factor for NAFLD in obese children. Our findings provided a novel approach of metformin administration for the prevention and treatment of NAFLD. This study also confirmed that metformin decreased the expression of hepatic THBS in DIO mice.