First Author | Venema W | Year | 2020 |
Journal | Front Cell Neurosci | Volume | 14 |
Pages | 140 | PubMed ID | 32528252 |
Mgi Jnum | J:342994 | Mgi Id | MGI:6729503 |
Doi | 10.3389/fncel.2020.00140 | Citation | Venema W, et al. (2020) Ciliary Neurotrophic Factor Acts on Distinctive Hypothalamic Arcuate Neurons and Promotes Leptin Entry Into and Action on the Mouse Hypothalamus. Front Cell Neurosci 14:140 |
abstractText | In humans and experimental animals, the administration of ciliary neurotrophic factor (CNTF) reduces food intake and body weight. To gain further insights into the mechanism(s) underlying its satiety effect, we: (i) evaluated the CNTF-dependent activation of the Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) pathway in mouse models where neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) neurons can be identified by green fluorescent protein (GFP); and (ii) assessed whether CNTF promotes leptin signaling in hypothalamic feeding centers. Immunohistochemical experiments enabled us to establish that intraperitoneal injection of mouse recombinant CNTF activated the JAK2-STAT3 pathway in a substantial proportion of arcuate nucleus (ARC) NPY neurons (18.68% +/- 0.60 in 24-h fasted mice and 25.50% +/- 1.17 in fed mice) but exerted a limited effect on POMC neurons (4.15% +/- 0.33 in 24-h fasted mice and 2.84% +/- 0.45 in fed mice). CNTF-responsive NPY neurons resided in the ventromedial ARC, facing the median eminence (ME), and were surrounded by albumin immunoreactivity, suggesting that they are located outside the blood-brain barrier (BBB). In both normally fed and high-fat diet (HFD) obese animals, CNTF activated extracellular signal-regulated kinase signaling in ME beta1- and beta2-tanycytes, an effect that has been linked to the promotion of leptin entry into the brain. Accordingly, compared to the animals treated with leptin, mice treated with leptin/CNTF showed: (i) a significantly greater leptin content in hypothalamic protein extracts; (ii) a significant increase in phospho-STAT3 (P-STAT3)-positive neurons in the ARC and the ventromedial hypothalamic nucleus of normally fed mice; and (iii) a significantly increased number of P-STAT3-positive neurons in the ARC and dorsomedial hypothalamic nucleus of HFD obese mice. Collectively, these data suggest that exogenously administered CNTF reduces food intake by exerting a leptin-like action on distinctive NPY ARC neurons and by promoting leptin signaling in hypothalamic feeding centers. |