mTORC1 and 2 Adrenergic Regulation and Function in Brown Adipose Tissue

Author(s)

Festuccia, William T.

• Document type: Journal article
• Source: PHYSIOLOGY; v. 40, n. 2, p. 11-pg., 2025-03-29.

Abstract

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)

• FAPESP's process: 19/01763-4 - Characterization of the molecular mechanisms determining the energy balance, glucose homeostasis and hepatomegaly in mice with severe lipodystrophy
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04159-8 - mTORC2 and mTORC1 biology and involvement in steatosis development and progression to steatohepatitis and hepatocellular carcinoma
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/19530-5 - Involvement of the nutrient sensor mTOR in the development of obesity associated chronic metabolic diseases
• Grantee: William Tadeu Lara Festuccia
• Support Opportunities: Research Projects - Thematic Grants