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PI3K in the VMH Attenuates Diet-Induced Obesity and Participates in the Effects of E2 on Energy Expenditure in Mice

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de Jesus, Aline Alves ; Dos-Santos, Raoni Conceicao ; Rodrigues-Santos, Isabelle ; Veida-Silva, Hellen ; Mata, Milene Mantovani ; Volpi, Rafaella Eduarda ; Goncalves, Gabriel Henrique Marques ; Navegantes, Luiz Carlos ; Elias, Carol Fuzeti ; Antunes-Rodrigues, Jose ; Elias, Lucila Leico Kagohara
Total Authors: 11
Document type: Journal article
Source: JOURNAL OF THE ENDOCRINE SOCIETY; v. 9, n. 7, p. 11-pg., 2025-07-01.
Abstract

Obesity is associated with the development of several illnesses, such as diabetes mellitus, cancer, and cardiovascular diseases. Elucidating the mechanisms of body weight control is important for the development of effective therapeutic strategies against obesity. In response to the action of hormones such as leptin and 17 beta-estradiol (E2), the ventromedial hypothalamus (VMH) plays an essential role in protection against diet-induced obesity (DIO) through the regulation of food intake and energy expenditure. However, little is known about the intracellular mechanisms involved in these effects. To assess the role of phosphoinositide 3-kinase (PI3K) signaling in neurons that express 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 the catalytic subunit P110 alpha in SF1 neurons in the VMH. We demonstrated that the conditional knockout of P110 alpha in SF1 neurons in the VMH affects body weight, energy expenditure, and thermogenesis in animals fed a high-fat diet. In addition, we demonstrated that female mice with genetic disruption of PI3K activity in VMH neurons exhibited greater weight gain than their male counterparts. Furthermore, inhibition of PI3K activity in the VMH partially blocked the effects of E2 on body weight regulation, stimulation of energy expenditure, and thermogenesis in female ovariectomized mice. Collectively, our results indicate that PI3K activity in VMH neurons plays a relevant role in protecting against DIO and contributes to the effects of estradiol on energy expenditure in females. (AU)

FAPESP's process: 20/07368-7 - PI3K role in the effects of estradiol on SF-1 neurons in the control of energy homeostasis
Grantee:Aline Alves de Jesus
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/18071-5 - Hydroelectrolytic and energy homeostasis: from cellular metabolism to endocrine systems in different phases of development
Grantee:Lucila Leico Kagohara Elias
Support Opportunities: Research Projects - Thematic Grants