Excess portal venous long-chain fatty acids induce syndrome X via HPA axisand sympathetic activation

We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistan ce via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the long-chai n fatty acid oleate (150 nmol/min, 24 h), the medium-chain fatty acid capry late, or the solvent. Corticosterone (Cort) and norepinephrine (NE) were me asured as indexes for HPA axis and sympathetic activity, respectively. Insu lin sensitivity was assessed by means of an intravenous glucose tolerance t est (IVGTT). Oleate infusion induced increases in plasma Cort (Delta = 13.5 +/- 3.6 mug/dl; P< 0.05) and NE (<Delta> = 235 +/- 76 ng/l; P< 0.05), wher eas caprylate and solvent had no effect. The area under the insulin respons e curve to the IVGTT was larger in the oleate-treated group than in the cap rylate and solvent groups (area = 220 +/- 35 vs. 112 +/- 13 and 106 +/- 8, respectively, P< 0.05). The area under the glucose response curves was comp arable [area = 121 +/- 13 (oleate) vs. 135 +/- 20 (caprylate) and 96 +/- 11 (solvent)]. The results are consistent with the concept that increased por tal free fatty acid is involved in the induction of visceral obesity-relate d insulin resistance via activation of the HPA axis and sympathetic system.