Increases in Adiponectin Predict Improved Liver, but Not Peripheral, Insulin Sensitivity in Severely Obese Women During Weight Loss

Abstract

Obesity-related glucose intolerance is a function of hepatic (homeostatic model assessment-insulin resistance [HOMA-IR]) and peripheral insulin resistance (Si) and β-cell dysfunction. We determined relationships between changes in these measures, visceral (VAT) and subcutaneous (SAT) adipose tissue, and systemic adipocytokine biomarkers 1 and 6 months after surgical weight loss. HOMA-IR decreased significantly (−50%) from baseline by 1 month and decreased further (−67%) by 6 months, and Si was improved by 6 months (2.3-fold) weight loss. Plasma concentrations of leptin decreased and adiponectin increased significantly by 1 month, and decreases in interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-α were observed at 6 months of weight loss. Longitudinal decreases in CRP (r = −0.53, P < 0.05) were associated with increases in Si, and decreases in HOMA-IR were related to increases in adiponectin (r = −0.37, P < 0.05). Decreases in VAT were more strongly related to increases in adiponectin and decreases in CRP than were changes in general adiposity or SAT. Thus, in severely obese women, specific loss of VAT leads to acute improvements in hepatic insulin sensitivity mediated by increases in adiponectin and in peripheral insulin sensitivity mediated by decreases in CRP.