| Grant number: | 15/25862-0 |
| Support type: | Scholarships in Brazil - Doctorate (Direct) |
| Effective date (Start): | June 01, 2016 |
| Effective date (End): | February 28, 2021 |
| Field of knowledge: | Biological Sciences - Biochemistry - Metabolism and Bioenergetics |
| Principal Investigator: | Alicia Juliana Kowaltowski |
| Grantee: | Pâmela Aiako Hypólito Brito Kakimoto |
| Home Institution: | Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
Abstract Increased production of intracellular oxidants due to nutrient overloading from diet has been linked to the development of metabolic diseases such as Nonalcoholic Fatty Liver Disease (NAFLD) and diabetes type 2. The inability of the adipose tissue to handle excess lipids can result in increased efflux of Non-Esterified Fatty Acids (NEFAs) and release of proinflammatory cytokines and adipokines that may result in ectopic fat deposition in the liver, muscle and heart. Mitochondrial lipid metabolism, when compared to carbohydrates, displays lower bioenergetic efficiency and increased production of reactive oxygen species. These functions, although fundamental for energy homeostasis and cellular redox signaling, may be involved in the development and progression of metabolic diseases. Oxidants, when exceeding cellular capacity to control and remove, may impair insulin signaling at both the level of the receptor and downstream, leading to resistance to its action. The cellular redox state is critical in the control of mitochondrial function, but, in addition, the activity of many metabolic enzymes and signaling processes is susceptible to oxidative modification. Consequently, understanding the actions of reactive species in metabolic control is important for uncovering the pathophysiological mechanisms of diet-associated metabolic diseases. In this project, we sought to evaluate the effects of obesity on the bioenergetic profile of murine hepatocytes, correlating to possible changes in the profile of redox signaling and insulin signaling. (AU) | |