Glial Endozepines Reverse High-Fat Diet-Induced Obesity by Enhancing Hypothalamic Response to Peripheral Leptin.

Molecular Neurobiology
Florent GuillebaudJean-Denis Troadec

Abstract

Research on energy homeostasis has focused on neuronal signaling; however, the role of glial cells has remained little explored. Glial endozepines exert anorexigenic actions by mechanisms which remain poorly understood. In this context, the present study was designed to decipher the mechanisms underlying the anorexigenic action of endozepines and to investigate their potential curative effect on high-fat diet-induced obesity. We carried out a combination of physiological, pharmacological, and molecular analyses together to dissect the underlying mechanisms of endozepine-induced hypophagia. To evaluate the potential anti-obesity effect of endozepines, different model of obesity were used, i.e., ob/ob and diet-induced obese mice. We show that the intracerebral administration of endozepines enhances satiety by targeting anorexigenic brain circuitry and induces STAT3 phosphorylation, a hallmark of leptin signaling. Strikingly, endozepines are entirely ineffective at reducing food intake in the presence of a circulating leptin antagonist and in leptin-deficient mice (ob/ob) but potentiate the reduced food intake and weight loss induced by exogenous leptin administration in these animals. Endozepines reversed high fat diet-induced ob...Continue Reading

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Citations

Oct 27, 2020·Glia·Bruno LebrunJean-Denis Troadec
Nov 5, 2020·Cells·Florent GuillebaudJean-Denis Troadec
Mar 17, 2021·Journal of Neuroendocrinology·Ismael González-GarcíaCristina García-Cáceres
Apr 8, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Matei Bolborea, Fanny Langlet
Aug 4, 2021·Open Biology·Joshua Wang, Kate Beecher
Jul 30, 2021·The Journal of Clinical Investigation·Tori LhommeVincent Prevot

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Datasets Mentioned

BETA
AB5733

Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
electron microscopy
nuclear translocation
PCR

Software Mentioned

Adobe Photoshop
ACT
Free
Mini Analysis
Dataquest ART
pClamp
NIH ImageJ
Synaptosoft

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