STAT3 but not ERK2 is a Crucial Mediator against Diet-Induced Obesity via VMH neurons

Leptin plays an important role in the protection against diet-induced obesity (DIO) by its actions in ventromedial hypothalamic (VMH) neurons. However, little is known about the intracellular mechanisms involved in these effects. To assess the role of the STAT3 and ERK2 signaling in neurons that exp...

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Bibliographic Details
Published in:	Diabetes (New York, N.Y.) Vol. 70; no. 7; pp. 1498 - 1507
Main Authors:	Gonçalves, Gabriel Henrique Marques, Trist O, Sabrina Mara, Volpi, Rafaella Eduarda, Almeida-Pereira, Gislaine, de Carvalho Borges, Beatriz, Donato, Jr, José, de Castro, Margaret, Antunes-Rodrigues, José, Elias, Lucila Leico Kagohara
Format:	Journal Article
Language:	English
Published:	United States American Diabetes Association 01-07-2021
Subjects:	Body weight Energy balance Energy expenditure Extracellular signal-regulated kinase Food intake Glucose High fat diet Homeostasis Hypothalamus Hypothalamus (ventromedial) Leptin Neurons Obesity Stat3 protein Steroidogenic factor 1
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Summary:	Leptin plays an important role in the protection against diet-induced obesity (DIO) by its actions in ventromedial hypothalamic (VMH) neurons. However, little is known about the intracellular mechanisms involved in these effects. To assess the role of the STAT3 and ERK2 signaling in neurons that express the steroidogenic factor 1 (SF1) in the VMH on energy homeostasis, we used cre-lox technology to generate male and female mice with specific disruption of STAT3 or ERK2 in SF1 neurons of the VMH. We demonstrated that the conditional knockout of STAT3 in SF1 neurons of the VMH did not affect body weight, food intake, energy expenditure and glucose homeostasis in animals on regular chow. However, when challenged with high-fat diet (HFD), loss of STAT3 in SF1 neurons caused a significant increase in body weight, food intake and energy efficiency that was more remarkable in females which also showed a decrease in energy expenditure. In contrast, deletion of ERK2 in SF1 neurons of VMH did not have any impact on energy homeostasis in both regular diet and HFD conditions. In conclusion, STAT3 but not ERK2 signaling in SF1 neurons of VMH plays a crucial role to protect against DIO in a sex-specific pattern.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0012-1797 1939-327X
DOI:	10.2337/db20-0658