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The role of non canonical NFkB pathway in Kupffer cells in the hepatic insulin resistance

Grant number: 13/07313-4
Support type:Scholarships abroad - Research
Effective date (Start): November 15, 2013
Effective date (End): November 14, 2014
Field of knowledge:Health Sciences - Nutrition
Principal researcher:Adriana Souza Torsoni
Grantee:Adriana Souza Torsoni
Host: Liangyou Rui
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Research place: University of Michigan, United States  

Abstract

The obesity has acquired epidemic characteristics and the same numbers that indicate the increase in obesity also showed a significant increase in individuals with diabetes mellitus type II. It is now known that both diseases exhibit a metabolic response characteristic, which leads to changes in intracellular signaling pathways and glucose homeostasis. High fat diet (HFD) consumption is responsible for the increased fat mass leading to an increased production of pro-inflammatory cytokines. Several studies indicate the involvement of macrophages in this process. The non-canonical NF-ºB pathway contributes to the pro-inflammatory signaling activation, and may represent a key metabolic pathway in response to obesity, especially in insulin resistance. Our hypothesis is that the nutritional overload trigger macrophage polarization in metabolic tissues and activation of NIK by blocking of TRAF-3 on immune cells (such as Kupffer cells), resulting in an increase in pro-inflammatory cytokines expression. To test this hypothesis, we will employ mice fed high fat diets with selective deficiency to NIK protein in cells of the myeloid lineage. The animals will be evaluated for hepatic insulin sensitivity in order to determine whether the deficiency on non-canonical NF-ºB pathway makes them protected from the effects of inflammation. Furthermore, co-culture of Kupffer cells and hepatocytes treated with TRAF-3 siRNA, adenovirus overexpressing NIK or palmitic acid will be performed in order to confirm the importance of communication between hepatocytes and macrophages residing in the liver in the development of insulin resistance. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
XIONG, YI; TORSONI, ADRIANA SOUZA; WU, FEIHUA; SHEN, HONG; LIU, YAN; ZHONG, XIAO; CANET, MARK J.; SHAH, YATRIK M.; OMARY, M. BISHR; LIU, YONG; RUI, LIANGYOU. Hepatic NF-kappa B-inducing kinase (NIK) suppresses mouse liver regeneration in acute and chronic liver diseases. eLIFE, v. 7, AUG 2 2018. Web of Science Citations: 2.

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