Ciliary neurotrophic factor suppresses hypothalamic AMP-kinase signaling in leptin-resistant obese mice

Abstract

We examined the actions of a second-generation ciliary neurotrophic factor analog (CNTFAx15) on AMP-activated protein kinase (AMPK), a known regulator of food intake. Unlike leptin CNTFAx15 has been shown to reduce food intake in obese rodents and humans. Intraperitoneal injection of CNTFAx15 acutely (45 min) reduced hypothalamic AMPKα2 activity, AMPKα2Thr172 phosphorylation, and acetyl-coenzyme A carboxylase phosphorylation, effects not observed 2 or 6 h after injection. Intracerebroventricular CNTFAx15 reduced food intake, increased arcuate nucleus (ARC) signal transducer and activator of transcription 3 phosphorylation, and reduced AMPK signaling but not in the paraventricular nucleus (PV..