Diet‐Induced Obesity Causes Selective Insulin Resistance

Abstract

Peripheral insulin resistance is a hallmark characteristic of the metabolic syndrome and obesity. However, whether obesity causes insulin resistance in brain is not known. To test this hypothesis, male Sprague‐Dawley rats (200–250g) were fed a moderately high‐fat diet (32% kcal as fat) or a low fat (LF) diet (10.6% kcal as fat). After 13 weeks, the body weights of rats fed the moderately high‐fat diet segregated into obesity‐prone (OP, 793±13 g) and obesity‐resistant (OR, 596±8 g) groups. The control group consisted of young adult rats (292±22 g, n=4) or rats fed LF (612±15 g, n=4). Rats were anesthetized with α‐chloralose and infused with insulin (3.75 mU/kg/min) and 50% dextrose (.25–.75 ml/hr) for 120 min. Baseline plasma insulin levels were significantly elevated in OP compared to OR and control rats (OP: 16±2 vs OR: 8±1 and control: 11±1 ng/ml, p<0.05). As expected, glucose utilization was significantly reduced in OP rats (OP: 3.3±0.7 vs OR: 5.5±0.9 and control: 7.5±0.8 mg/kg/min, p<0.05). Interestingly, hyperinsulinemia produced similar increases in lumbar sympathetic nerve activity across groups (OP: 127±6%; OR: 128±9%, control: 133±10% P>0.05). Arterial blood pressure decreased significantly by 120 min in all groups (OP: 94±4 vs 84±3 mmHg; OR: 94±7 vs 87±6 mmHg, control: 100±7 vs 85±6, P<0.05). These findings indicate that obesity causes peripheral but not central insulin resistance.Supported by NIH HL090826, AHA 0630202N & 0815372D