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

Author(s)

Goncalves, Gabriel Henrique Marques ^{[1, 2]} ; Tristao, Sabrina Mara ^[1] ; Volpi, Rafaella Eduarda ^[1] ; Almeida-Pereira, Gislaine ^[1] ; de Carvalho Borges, Beatriz ^[1] ; Donato, Jr., Jose ^[3] ; de Castro, Margaret ^[2] ; Antunes-Rodrigues, Jose ^[1] ; Elias, Lucila Leico Kagohara ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Physiol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Div Endocrinol & Metab, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil

• Document type: Journal article
• Source: Diabetes; v. 70, n. 7, p. 1498-1507, JUL 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 14/17248-8 - Role of STAT3 and ERK in SF1 neurons of hypothalamus in the effects of leptin and estradiol on energy homeostasis
• Grantee: Lucila Leico Kagohara Elias
• Support type: Regular Research Grants
• FAPESP's process: 18/10090-0 - Role of STAT3 and PI3K signaling in SF1 neurons of the hypothalamus on energy homeostasis
• Grantee: Gabriel Henrique Marques Gonçalves
• Support type: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/09799-1 - Energy balance and body fluid homeostasis control: from cells to the physiological systems
• Grantee: José Antunes Rodrigues
• Support type: Research Projects - Thematic Grants