Adipocyte-Specific FAK Deletion in Mice Leads to Insulin Resistance but Divergent Adipose Tissue Remodelling Under Lean and Obese Conditions

Abstract

Insulin resistance and liver fat are both predictors of type 2 diabetes (T2D) in youth. Although lean body mass (LBM) is known to influence insulin resistance, the association of LBM with liver fat has received little attention in youth at risk of T2D. To investigate the association between insulin resistance and liver fat with LBM in youth at risk of T2D. 113 overweight and obese (97.1±3.1 BMI percentile) youth (15.3±1.7 years) participated in this cross-sectional study. The primary outcome measures were insulin resistance (measured by HOMA-IR), liver transaminases (ALT/AST), and liver fat (MRS measured). The primary exposure variable was LBM index [LBMI; lean body mass (kg)/height (m2)]. LBMI was positively associated with fat mass (r=0.56, p=0.0001) and visceral fat mass (r=0.39, p=0.0001). LBMI was negatively associated with HDL-cholesterol (r=–0.28, p=0.006) and positively associated with AST (r=0.27, p=0.002), ALT (r=0.46, p=0.0001), and liver fat (r=0.28, p=0.002). Multiple linear regressions revealed that LBMI was associated with HOMA-IR (ß=0.216 SE 0.061, p=0.0006) and ALT (ß=1.557 SE 0.482, p=0.001) independently of age, sex, ethnicity, visceral fat mass and fitness level, but not with liver fat (p=0.186). These results suggest that LBMI contributes to insulin resistance and liver fat in youth at risk of T2D. Considering that liver fat is the strongest predictor of T2D in youth, LBMI should be considered in risk assessment in youth at high risk of T2D.