Intrahepatic Fat, Not Visceral Fat, is Associated with Liver, Muscle and Adipose Tissue Insulin Resistance in Obese Subjects
Abstract Number: 76-LB
Authors: ELISA FABBRINI, SELMA B. MOHAMMED, KEVIN KORENBLAT, SAMUEL KLEIN, St Louis, MO
Institutions: St Louis, MO
Results: Both increased visceral fat (VF) and increased intrahepatic fat (IHF) are associated with insulin resistance and diabetes. However, it is not clear whether VAT or IHF are independent risk factors for insulin resistance, because an increase in one fat depot is usually correlated with an increase in the other. Therefore, we evaluated insulin action in liver (glucose production), skeletal muscle (glucose uptake), and adipose tissue (lipolysis) in 3 groups of obese subjects (BMI range: 29-45 kg/m2) who were matched on either VF volume or IHF content: 1) normal IHF (3.7±1.8%) and high IHF (25.3±11%) (n=10 for each group), matched on VF volume (1290±754 and 1335±564 cm3); 2) low VF (744±276 cm3) and high VF (1474±840 cm3), with normal IHF content (3.7±2% and 3.4±2%) (n=7 in each group); and 3) low VF (1093±372 cm3) and high VF (2112±1070 cm3), with high IHF content (21±15% and 22±12%) (n=7 in each group). In all studies, subjects were matched on sex, body mass index, and percent body fat. A euglycemic-hyperinsulinemic clamp procedure in conjunction with stable isotope tracer infusion, were used to assess hepatic, muscle, and adipose tissue insulin sensitivity. Magnetic resonance spectroscopy and magnetic resonance imaging were used to detect IHF content and VF volume, respectively. Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration, was 41±11% higher in subjects with low IHF than those with high IHF, matched on VF volume (p<0.01). Adipose tissue insulin sensitivity, assessed as the decrease in palmitate release into plasma during insulin infusion, was greater in subjects with low IHF than those with high IHF, matched on VF volume (72±2% vs 62±3% reduction from basal, p<0.01). Muscle insulin sensitivity, assessed as the increase in glucose uptake during insulin infusion, was greater in subjects with low IHF than those with high IHF, matched on VF volume (273±28% vs 175±6% increase from basal, p<0.05). However, differences in VF volume did not affect adipose tissue, liver, or skeletal muscle insulin sensitivity when subjects were matched on IHF content. These data demonstrate that IHF content, not VF volume, is associated with liver, adipose tissue, and skeletal muscle insulin resistance in obese non-diabetic subjects. The relationship between VF volume and insulin resistance observed in previous studies might be due to the correlation between VF and IHF.
Category: Obesity - Human