Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai jiang Yu, Rui tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E. Scherer, Tiemin Liu, Kevin W. Williams

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Objective Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation – including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined. Methods In order to resolve this issue, we utilized neuron-specific transgenic mouse models to identify Pomc and NPY/AgRP neurons which express LepRs for patch-clamp electrophysiology experiments. Results We found that leptin and adiponectin synergistically activated melanocortin neurons in the arcuate nucleus. Conversely, NPY/AgRP neurons were inhibited in response to adiponectin. The adiponectin-induced depolarization of arcuate Pomc neurons occurred via activation of Phosphoinositide-3-kinase (PI3K) signaling, independent of 5′ AMP-activated protein kinase (AMPK) activity. Adiponectin also activated melanocortin neurons at various physiological glucose levels. Conclusions Our results demonstrate a requirement for PI3K signaling in the acute adiponectin-induced effects on the cellular activity of arcuate melanocortin neurons. Moreover, these data provide evidence for PI3K as a substrate for both leptin and adiponectin to regulate energy balance and glucose metabolism via melanocortin activity.

Original languageEnglish (US)
Pages (from-to)882-891
Number of pages10
JournalMolecular Metabolism
Volume5
Issue number10
DOIs
StatePublished - Oct 1 2016

Keywords

  • Diabetes
  • Electrophysiology
  • Energy balance
  • Melanocortin
  • Obesity
  • Patch-clamp

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Sun, J., Gao, Y., Yao, T., Huang, Y., He, Z., Kong, X., Yu, K. J., Wang, R. T., Guo, H., Yan, J., Chang, Y., Chen, H., Scherer, P. E., Liu, T., & Williams, K. W. (2016). Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons. Molecular Metabolism, 5(10), 882-891. https://doi.org/10.1016/j.molmet.2016.08.007