title: Central prolactin receptors (PRLRs) regulate hepatic insulin sensitivity in mice via signal transducer and activator of transcription 5 (STAT5) and the vagus nerve.
abstract: OBJECTIVE
  Recent studies have revealed the crucial role of the central nervous system (CNS), especially the hypothalamus, in the regulation of insulin sensitivity in peripheral tissues. The aim of our current study was to investigate the possible involvement of hypothalamic prolactin receptors (PRLRs) in the regulation of hepatic insulin sensitivity.
  
  
  METHODS
  We employed overexpression of PRLRs in mouse hypothalamus via intracerebroventricular injection of adenovirus expressing PRLR and inhibition of PRLRs via adenovirus expressing short-hairpin RNA (shRNA) specific for PRLRs in vivo. Selective hepatic vagotomy was employed to verify the important role of the vagus nerve in mediating signals from the brain to peripheral organs. In addition, a genetic insulin-resistant animal model, the db/db mouse, was used in our study to investigate the role of hypothalamic PRLRs in regulating whole-body insulin sensitivity.
  
  
  RESULTS
  Overexpression of PRLRs in the hypothalamus improved hepatic insulin sensitivity in mice and inhibition of hypothalamic PRLRs had the opposite effect. In addition, we demonstrated that hypothalamic PRLR-improved insulin sensitivity was significantly attenuated by inhibiting the activity of signal transducer and activator of transcription 5 (STAT5) in the CNS and by selective hepatic vagotomy. Finally, overexpression of PRLRs significantly ameliorated insulin resistance in db/db mice.
  
  
  CONCLUSIONS
  Our study identifies a novel central pathway involved in the regulation of hepatic insulin sensitivity, mediated by hypothalamic PRLR/STAT5 signalling and the vagus nerve, thus demonstrating an important role for hypothalamic PRLRs under conditions of insulin resistance.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, People's Republic of China.
authors: Fei
authors: F
authors: Xiao
authors: Tingting
authors: T
authors: Xia
authors: Ziquan
authors: Z
authors: Lv
authors: Qian
authors: Q
authors: Zhang
authors: Yuzhong
authors: Y
authors: Xiao
authors: Junjie
authors: J
authors: Yu
authors: Hao
authors: H
authors: Liu
authors: Jiali
authors: J
authors: Deng
authors: Yajie
authors: Y
authors: Guo
authors: Chunxia
authors: C
authors: Wang
authors: Kai
authors: K
authors: Li
authors: Bin
authors: B
authors: Liu
authors: Shanghai
authors: S
authors: Chen
authors: Feifan
authors: F
authors: Guo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007031:Hypothalamus / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor