Elsevier

Molecular Metabolism

Volume 5, Issue 10, October 2016, Pages 882-891
Molecular Metabolism

Original article
Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

https://doi.org/10.1016/j.molmet.2016.08.007Get rights and content
Under a Creative Commons license
open access

Highlights

  • Adiponectin activates arcuate Pomc neurons.

  • Adiponectin-induced activation of Pomc neurons requires PI3K (independent of AMPK).

  • Adiponectin inhibits adjacent NPY/AgRP neurons (disinhibiting arcuate Pomc neurons).

  • Leptin potentiates the effects of adiponectin arcuate Pomc neurons.

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.

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Keywords

Melanocortin
Obesity
Diabetes
Energy balance
Patch-clamp
Electrophysiology

Cited by (0)

9

Jia Sun, Yong Gao, Ting Yao are co-first authors.