Analysis of the effects of chronic central treatment with irisin on hepatic lipid metabolism in mice subjected to the diet-induced obesity model

• Grant number: 24/04650-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Helena Cristina de Lima Barbosa
• Grantee: Guilherme Santos de Freitas
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/04664-7 - Molecular mechanisms involved in pancreatic beta cell dysfunction and death in Diabetes Mellitus: strategies for the inhibition of these processes and restoration of the insular mass, AP.TEM

Abstract

Obesity is a medical condition with numerous damages to human health, being correlated to several metabolic changes and showing continuous growth over the years, mainly due to unhealthy eating habits and a sedentary lifestyle. Side effects of a high-fat, high-calorie diet may include accumulation of triglycerides and cholesterol in the liver, increased insulin resistance, chronic inflammatory status, and dyslipidemia. In this context, the liver becomes a relevant target in studies to understand the mechanisms and possible strategies for controlling obesity, since it metabolically processes carbohydrates, fats, and proteins. The central nervous system controls the body's energy homeostasis, with the hypothalamus being responsible for controlling the autonomic and endocrine nervous systems, having nuclei with different functions for transmitting information to peripheral organs, such as the liver. Irisin, an adipomyokine secreted after exercise, is related to several metabolic benefits conferred by exercise, including the control of hepatic metabolism. There is evidence that suggests its effects on the central nervous system, and it may act in the control of hepatic lipid metabolism through a central mechanism of action, participating in the modulation of energy metabolism, and contributing to obesity control and prevention strategies. In this sense, the present project aims to identify the effects of chronic intracerebroventricular (ICV) treatment with irisin, in mice subjected to the obesity model induced by a high-fat diet, on hepatic lipid metabolism. For this, male C57BL/6 mice will be fed a high-fat diet (45%), to induce obesity, and treated via ICV with irisin 300 ng/day, for 7 days. Body weight, liver, and white adipose tissue mass will be assessed; the expression of genes involved in the regulation of lipogenesis (FAS, ACC, SCD1, SREBP1c) and lipolysis (PPARalpha, HSL, CPT-1, and ACO) will be evaluated in the liver by RT-qPCR; liver morphology and the presence of steatosis will be assessed through histological sections of the liver; and triglyceride and cholesterol concentrations in liver and plasma samples will be assessed using enzymatic kits. This project will contribute to a better understanding of the hepatic repercussions associated with the central effect of irisin in an obesity model.