Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system

Baile Wang, Ang Li, Xiaomu Li, Philip W.L. Ho, Donghai Wu, Xiaoqi Wang, Zhuohao Liu, Kelvin K.L. Wu, Sonata S.Y. Yau, Aimin Xu, Kenneth K.Y. Cheng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

16 Citations (Scopus)


Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT. Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2–AMPK signaling axis is crucial for this defending mechanism to cold and obesity.

Original languageEnglish
Article numbere44977
JournalEMBO Reports
Issue number4
Early online date21 Feb 2018
Publication statusPublished - Apr 2018


  • AMPK
  • beiging
  • hypothalamus
  • obesity
  • sympathetic nervous system

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this