| Grant number: | 21/14419-0 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | April 01, 2022 |
| End date: | March 31, 2027 |
| Field of knowledge: | Biological Sciences - Physiology - Physiology of Organs and Systems |
| Principal Investigator: | William Tadeu Lara Festuccia |
| Grantee: | Bianca Franco Leonardi |
| 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 |
| Associated scholarship(s): | 24/06344-8 - Evaluation of mTORC2 role as a mediator of LPS inflammatory and metabolic actions in liver using a perfusable liver-on-a-chip system, BE.EP.PD |
Abstract Non-alcoholic fatty liver disease (NAFLD) is a group of highly prevalent liver diseases that comprises from a simple steatosis (NAFL) to more severe conditions such as steatohepatitis (NASH), cirrhosis and hepatocarcinome (HCC). Despite the recent advances in NAFLD physiopathology, the molecular mechanisms and signaling pathways that contribute to NAFLD onset and progression are not completely understood. Several pieces of evidence indicate that intestinal dysbiosis and lipopolysaccharides (LPS) play a major role in NAFLD onset and progression exacerbating lipid deposition, inflammation, oxidative stress, mitochondrial dysfunction, among other phenotypes commonly found upon NAFLD. Therefore, in the current proposal, we will investigate the involvement of Rictor/mTORC2 as a mediator of LPS actions in the development of NAFLD induced by intake of diet rich in fructose. For this, C57BL6/J mice bearing or not Rictor/mTORC2 deficiency in either hepatocytes (Albumin Cre) or macrophages (lysozyme M Cre) will be fed with either a control or a high fructose diet and acutely (30, 120 e 240 min) or chronically (28 days) treated with LPS. After this period, mice will be evaluated for body weight, adiposity, glucose homeostasis, liver mass, morphology, lipid and glycogen contents and lipidome, intracellular signaling, gene expression, autophagy, mitochondrial function, de novo lipogenesis, glucose and fatty acid oxidation, triacylglycerol secretion, oxidative stress and antioxidant enzymes, among other variables. In vitro experiments will be conducted with primary hepatocytes and Kupffer cells bearing or not Rictor/mTORC2 deficiency in mono- or co-culture after treatment with LPS or vehicle. Cells will be evaluated for intracellular signaling, lipid and glucose metabolism, autophagy and cytokine secretion. | |
| News published in Agência FAPESP Newsletter about the scholarship: | |
| More itemsLess items | |
| TITULO | |
| Articles published in other media outlets ( ): | |
| More itemsLess items | |
| VEICULO: TITULO (DATA) | |
| VEICULO: TITULO (DATA) | |