Chronic infusion of norepinephrine into the VMH of normal rats induces theobese glucose-intolerant state

Increases in ventromedial hypothalamic (VMH) norepinephrine (NE) levels and /or activities have been observed in a variety of animal models of the obes e insulin-resistant condition. This study examined the metabolic effects of chronic NE infusion (25 nmol/h) into the unilateral VMH of normal rats. Wi thin 4 days, VMH NE infusion significantly increased plasma insulin (140%), glucagon (45%), leptin (300%), triglyceride (100%), abdominal fat pad weig ht (50%), and white adipocyte lipogenic (100%) and lipolytic (100%) activit ies relative to vehicle-infused rats. Furthermore, isolated islet insulin s ecretory response to glucose (15 mM) within 4 days of such treatment was in creased over twofold (P < 0.05). Among treated animals, fat stores continue d to increase over time and plateaued at similar to 2 wk (3-fold increase), remaining elevated to the end of the study (5 wk). By week 4 of treatment, NE infusion induced glucose intolerance as evidenced by a 32% increase in plasma glucose total area under the glucose tolerance test curve (P < 0.01) . Whole body fat oxidation rate measured after 5 wk of infusion was signifi cantly increased among treated animals as evidenced by a reduced respirator y quotient (0.87 +/- 0.01) relative to controls (0.90 +/- 0.01). VMH NE inf usion induced hyperphagia (30%) only during the first week and did not affe ct body weight over the 5-wk period. Increases in VMH NE activity that are common among obese insulin-resistant animal models can cause the developmen t of this obese glucose-intolerant (metabolic) syndrome.