Effects of LPS on mass, morphology and intracellular signaling in white adipose tissue: study of mTORC2 involvement

• Grant number: 22/15153-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: July 31, 2024
• 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

Obesity is a risk factor for several non-communicable chronic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). Intake of a high-fat, high caloric diet increases the storage of fatty acids as triacylglycerol in adipocytes promoting firstly hypertrophy, followed by hyperplasia and expansion of white adipose tissue mass. Several studies have observed that obesity is associated with an increase in intestinal permeability and, consequently, the absorption of LPS, a component of the membrane of gram-negative bacteria present in the intestinal microbiota. Despite inducing inflammation by activating signaling through TLR4-NFkB and NLRP3-inflammasome pathways, previous studies have found that low levels of LPS increase, through unknown mechanisms, the number of small adipocytes in the subcutaneous white adipose tissue of mice. Considering the previous findings that LPS increases the activity of both mTORC1 and mTORC2, protein complexes that are involved in the control of proliferation, differentiation and metabolism of adipocytes, we will investigate herein the acute and chronic effects of two doses of LPS on mice body weight, food intake, and white adipose tissue mass, morphology, and intracellular signaling on mTORC1 and mTORC2 pathways. In a second protocol, we will also investigate the envolviment of Rictor, a protein which is essential to mTORC2 activity, as a mediator of LPS actions in the white adipose tissue.