mTORC1 and 2 Adrenergic Regulation and Function in Brown Adipose Tissue

Autor(es)

Festuccia, William T.

• Tipo de documento: Artigo Científico
• Fonte: PHYSIOLOGY; v. 40, n. 2, p. 11-pg., 2025-03-29.

Resumo

Brown adipose tissue (BAT) thermogenesis results from the uncoupling of mitochondrial inner membrane proton gradient mediated by uncoupling protein 1 (UCP-1), which is activated by lipolysis-derived fatty acids. Norepinephrine (NE) secreted by sympathetic innervation not only activates BAT lipolysis and UCP-1 but, uniquely in brown adipocytes, promotes "futile" metabolic cycles and enhances BAT thermogenic capacity by increasing UCP-1 content, mitochondrial biogenesis, and brown adipocyte hyperplasia. NE exerts these actions by triggering signaling in the canonical G protein-coupled beta-adrenergic receptors, cAMP, and protein kinase A (PKA) pathway, which in brown adipocytes is under a complex and intricate cross talk with important growth-promoting signaling pathways such as those of mechanistic target of rapamycin (mTOR) complexes 1 (mTORC1) and 2 (mTORC2). This article reviews evidence suggesting that mTOR complexes are modulated by and participate in the thermogenic, metabolic, and growth-promoting effects elicited by NE in BAT and discusses current gaps and future directions in this field of research. (AU)

• Processo FAPESP: 19/01763-4 - Caracterização dos mecanismos moleculares determinantes do equilíbrio energético, homeostase da glicose e hepatomegalia em camundongos lipodistróficos
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/04159-8 - Biologia e envolvimento de mTORC2 e mTORC1 no desenvolvimento da esteatose hepática e progressão para esteatohepatite e hepatocarcinoma
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/19530-5 - Caracterização do envolvimento do sensor de nutrientes mTOR no desenvolvimento de doenças metabólicas crônicas associadas à obesidade
• Beneficiário: William Tadeu Lara Festuccia
• Modalidade de apoio: Auxílio à Pesquisa - Temático