Neurogenesis in the Hypothalamus of Adult Mice: Potential Role in Energy Balance

TLDR

CNTF induces weight loss in obese rodents and humans, yet the mechanism underlying the persistence of this effect after treatment cessation remains unclear. Co‑administration of the mitotic blocker Ara‑C abolishes CNTF‑induced neural proliferation and eliminates its long‑term, but not short‑term, weight‑loss effect, indicating that sustained weight regulation requires hypothalamic cell division. CNTF stimulates proliferation in hypothalamic feeding centers, producing newborn neurons that express neuronal markers, respond to leptin via STAT3 phosphorylation, and thereby link hypothalamic neurogenesis to long‑term energy‑balance control.

Abstract

Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans, and for reasons that are not understood, its effects persist after the cessation of treatment. Here we demonstrate that centrally administered CNTF induces cell proliferation in feeding centers of the murine hypothalamus. Many of the newborn cells express neuronal markers and show functional phenotypes relevant for energy-balance control, including a capacity for leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Coadministration of the mitotic blocker cytosine-beta-d-arabinofuranoside (Ara-C) eliminates the proliferation of neural cells and abrogates the long-term, but not the short-term, effect of CNTF on body weight. These findings link the sustained effect of CNTF on energy balance to hypothalamic neurogenesis and suggest that regulated hypothalamic neurogenesis in adult mice may play a previously unappreciated role in physiology and disease.