Elsevier

Molecular Metabolism

Volume 5, Issue 8, August 2016, Pages 669-679
Molecular Metabolism

Original article
Leptin and insulin engage specific PI3K subunits in hypothalamic SF1 neurons

https://doi.org/10.1016/j.molmet.2016.06.004Get rights and content
Under a Creative Commons license
open access

Highlights

  • Leptin recruits p110β/TRPC channels to depolarize/activate SF1 neurons.

  • Leptin recruits p110α/p110β/KATP channels to hyperpolarize/inhibit SF1 neurons.

  • Insulin recruits p110α/p110β/KATP channels to hyperpolarize/inhibit SF1 neurons.

  • Acute leptin and insulin responses are segregated to distinct subsets of VMH SF1 neurons.

Abstract

Objective

The ventromedial hypothalamic nucleus (VMH) regulates energy balance and glucose homeostasis. Leptin and insulin exert metabolic effects via their cognate receptors expressed by the steroidogenic factor 1 (SF1) neurons within the VMH. However, detailed cellular mechanisms involved in the regulation of these neurons by leptin and insulin remain to be identified.

Methods

We utilized genetically-modified mouse models and performed patch-clamp electrophysiology experiments to resolve this issue.

Results

We identified distinct populations of leptin-activated and leptin-inhibited SF1 neurons. In contrast, insulin uniformly inhibited SF1 neurons. Notably, we found that leptin-activated, leptin-inhibited, and insulin-inhibited SF1 neurons are distinct subpopulations within the VMH. Leptin depolarization of SF1 neuron also required the PI3K p110β catalytic subunit. This effect was mediated by the putative transient receptor potential C (TRPC) channel. On the other hand, hyperpolarizing responses of SF1 neurons by leptin and insulin required either of the p110α or p110β catalytic subunits, and were mediated by the putative ATP-sensitive K+ (KATP) channel.

Conclusions

Our results demonstrate that specific PI3K catalytic subunits are responsible for the acute effects of leptin and insulin on VMH SF1 neurons, and provide insights into the cellular mechanisms of leptin and insulin action on VMH SF1 neurons that regulate energy balance and glucose homeostasis.

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Keywords

Cellular mechanism
Conditional knockout mouse
Patch clamp technique
Functional heterogeneity
Homeostasis

Cited by (0)

5

These authors are co-senior authors.