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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Diabetes; v. 70, n. 7, p. 1498-1507, JUL 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/17248-8 - Participação de STAT3 e ERK em neurônios SF1 do hipotálamo sobre os efeitos do estradiol e da leptina na homeostase energética
• Beneficiário: Lucila Leico Kagohara Elias
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/10090-0 - Participação de STAT3 e PI3K em neurônios SF1 do hipotálamo na homeostase energética
• Beneficiário: Gabriel Henrique Marques Gonçalves
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 13/09799-1 - Regulação da homeostase energética e do balanço hidromineral: das células aos sistemas fisiológicos
• Beneficiário: José Antunes Rodrigues
• Modalidade de apoio: Auxílio à Pesquisa - Temático