Ciliary neurotrophic factor prevents acute lipid-induced insulin resistance by attenuating ceramide accumulation and phosphorylation of c-Jun N-terminal kinase in peripheral tissues

Abstract

Ciliary neurotrophic factor (CNTF) is a member of the gp130 receptor cytokine family recently identified as an antiobesity agent in rodents and humans by mechanisms that remain unclear. We investigated the impact of acute CNTF treatment on insulin action in the presence of lipid oversupply. To avoid confounding effects of long-term high-fat feeding or genetic manipulation on whole-body insulin sensitivity, we performed a 2-h Intralipid infusion (20% heparinized Intralipid) with or without recombinant CNTF pretreatment (Axokine 0.3 mg/kg), followed by a 2-h hyperinsulinemic-euglycemic clamp (12 mU/kg·min) in fasted, male Wistar rats. Acute Intralipid infusion increased plasma free fatty acid ..