2013 Fiscal Year Final Research Report

Elucidation of amelioration mechanisms of metabolic endotoxemia induced insulin resistance by valsartan

Research Project

Project/Area Number	24792328
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Periodontal dentistry
Research Institution	Hiroshima University
Principal Investigator	IWASHITA Misaki 広島大学, 医歯薬保健学研究院(歯), 助教 (80611326)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	脂肪細胞 / マクロファージ / インスリン抵抗性 / アンジオテンシンII受容体拮抗薬
Research Abstract	In this study, we analyzed the gene expression profile of adipocytes co-cultured with lipopolysaccharide (LPS)-treated macrophages in the presence or absence of the angiotensin receptor 1 blocker valsartan. The genes of which expressions were affected by LPS-treated macrophages but normalized by co-addition of valsartan. Additionally, we analyzed the in vivo effects of valsartan, using mice constitutively infused with LPS. Oral administration of valsartan to LPS-infused mice normalized the increased expressions of inflammatory cytokines in adipose and liver tissues. In light of these data, it is reasonable to consider valsartan to normalize altered gene expression patterns in adipose tissue infiltrated by macrophages, and to ameliorate inflammation. These results raise the possibility that valsartan not only contributes to normalization of obesity-related insulin resistance, but is also beneficial for the treatment of other diseases with inflammation related to the metabolic syndrome.