STAT3 but Not ERK2 Is a Crucial Mediator Against Diet-Induced Obesity via VMH Neurons.

Abstract

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 in 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, or glucose homeostasis in animals on regular chow. However, with high-fat diet (HFD) challenge, 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 in protection against DIO in a sex-specific pattern.

• Authors: Gabriel Henrique Marques Gonçalves, Sabrina Mara Tristão, Rafaella Eduarda Volpi, Gislaine Almeida-Pereira, Beatriz de Carvalho Borges, José Donato, Margaret de Castro, José Antunes-Rodrigues, Lucila Leico Kagohara Elias
• Journal: Diabetes (Diabetes) Vol. 70 Issue 7 Pg. 1498-1507 (07 2021) ISSN: 1939-327X [Electronic] United States
• PMID: 33883215 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by the American Diabetes Association.

Chemical References

• RNA Splicing Factors
• STAT3 Transcription Factor
• Sf1 protein, mouse
• Stat3 protein, mouse
• Steroidogenic Factor 1
• steroidogenic factor 1, mouse
• Mapk1 protein, mouse
• Mitogen-Activated Protein Kinase 1

Topics

• Animals
• Diet, High-Fat
• Energy Metabolism
• Female
• Male
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinase 1 (physiology)
• Obesity (prevention & control)
• RNA Splicing Factors (physiology)
• STAT3 Transcription Factor (physiology)
• Sex Characteristics
• Steroidogenic Factor 1 (physiology)
• Ventromedial Hypothalamic Nucleus (physiology)