Adrenergic regulation of de novo fatty acids synthesis in brown adipose tissue: role of mTORC2 and 1

• Grant number: 24/13040-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: November 01, 2024
• End date: August 31, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: William Tadeu Lara Festuccia
• Grantee: Marina Akemi Abe Honda
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 20/04159-8 - mTORC2 and mTORC1 biology and involvement in steatosis development and progression to steatohepatitis and hepatocellular carcinoma, AP.TEM

Abstract

Futile metabolic cycles composed of antagonic processes such as fatty acids de novo synthesis and ²-oxidation are activated simutaneoulsy with brown adipose tissue UCP-1 and thermogenesis. Thus, it is our goal in this proposal to invetigate the signaling pathways regulating fatty acids de novo synthesis and ²-oxidation in brown adipose tissue with a special focus on the role of mTORC2 and 1 as mediators of adrenergic signaling. We will also investigate the contribution and impact of fatty acids de novo synthesis and ²-oxidation metabolic cycle to brown adipose tissue fatty acid profile, lipidome and thermogenic capacity and whole body energy balance and expenditure. For this, we will perform 3 protocols to invetigate the impact of: 1- unilateral brown adipose tissue sympathetic denervation; 2- adipocyte mTORC2 and mTORC1 deficiencies; and 3- pharmacological inhibition of acetyl-CoA carboxylase (ACC) e fatty acid synthase (FAS) on body weight, food intake, energy expenditure, core temperature, thermogenic capacity, histology (H/E), mass, DNA and triacylglycerol contents, intracelular signalling, de novo lipogenesis, ²-oxidation, mitochondrial mass and function, fatty acid profile and lipidome in the brown adipose tissue of mice kept at thermoneutrality (30ºC) or exposed to acute (10ºC, 6 and 24 h) or chronic (10ºC, 14 days) cold.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CASTRO, ERIQUE; VIEIRA, THAYNA S.; PEIXOTO, ALBERT S.; LEONARDI, BIANCA F.; TOMAZELLI, CAROLINE A.; LINO, CAROLINE A.; OLIVEIRA, TIAGO E.; PESSOA, NATALIA M.; PESSOA, ERIKA V. M.; ABE-HONDA, MARINA A.; et al. Fish Oil and EPA Improve Insulin Sensitivity, in Part Through Adipocyte mTORC2 Activation in Diet-Induced Obese Male Mice. MOLECULAR NUTRITION & FOOD RESEARCH, v. N/A, p. 14-pg., 2025-02-17. (19/00726-8, 24/13040-5, 21/14419-0, 19/01763-4, 22/11234-1, 23/04509-7, 22/02123-1, 23/04753-5, 18/11156-5, 20/04159-8, 19/04271-5, 15/19530-5, 16/23169-9, 20/16656-6, 22/00324-0)