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Effect of metformin on macrophage polarization and activation of AMPK in white adipose tissue, brown adipose tissue and muscle of obese animals

Grant number: 16/11466-9
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): October 01, 2016
Effective date (End): September 30, 2017
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Mario Jose Abdalla Saad
Grantee:Arthur Geise
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The increase in obesity in the national and world panorama is of great importance to public health, because it is closely associated with the development of chronic diseases, mainly diabetes mellitus type 2 (DM2). Obesity causes a state of chronic inflammation, triggered by the white adipose tissue (WAT) and their resident macrophages. Excess free fatty acids, LPS and inflammatory cytokines lead to the macrophage classical/M1activation in TAB and liver tissue, exacerbating the inflammatory state and local induced inhibition of insulin receptor substrate (IRS), increasing insulin resistance. On the other hand, the alternative/M2 polarization of macrophages, modulated by AMPK enzyme and brown adipose tissue (BAT), causes an anti-inflammatory action, improving insulin response. The action of AMPK is also associated with glucose uptake in muscle tissue and TAM, by an insulin-independent pathway, promoting thermogenesis and lipolysis in TAM in TAB. These functions of AMPK, added to their participation in the formation of TAM and an intermediate tissue between TAB and TAM, which also has thermogenic capacity, will be surveyed in this study, in order to clarify the mechanisms of weight loss conferred by the enzyme. Materials and methods: divide 3 groups of mice: one control, a high-fat diet (HFD) and HFD + metformin. The extraction of muscle and fat tissues will be followed by immunoblotting protein analysis. The analysis by optical microscopy uses immunohistochemistry and immunofluorescence. Inflammatory cytokines and catecholamines circulating levels will also be evaluated. (AU)