title: Valsartan restores inflammatory response by macrophages in adipose and hepatic tissues of LPS-infused mice.
abstract: Inflammation involving adipose tissue is regarded as one of the major molecular mechanisms underlying obesity-related insulin resistance. Recent studies have suggested a series of angiotensin II receptor blockers (ARBs) to improve insulin resistance or protect against the development of diabetes mellitus. We previously demonstrated that valsartan suppresses the inflammatory response of macrophages. Interestingly, however, this effect did not occur via peroxisome proliferator-activated receptor (PPAR) γ or the AT1a receptor. This suppression appears to secondarily lead to amelioration of insulin resistance and reductions in abnormal gene expressions in adipocytes. In addition to these in vitro findings, we herein demonstrate the in vivo effects of valsartan, using mice constitutively infused with lipopolysaccharide (LPS) for 4 weeks. Oral administration of valsartan to LPS-infused mice normalized the increased expressions of inflammatory cytokines in adipose and liver tissues. 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 such as atherosclerosis and non-alcoholic steatohepatitis. Further study is necessary to clarify these issues.
authors.affiliation: Department of Medical Chemistry; Division of Molecular Medical Science; Graduate School of Biomedical Sciences; Hiroshima University; Hiroshima, Japan ; Department of Dental Science for Health Promotion; Division of Cervico-Gnathostomatology; Graduate School of Biomedical Sciences; Hiroshima University; Hiroshima, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Iwashita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.forename: Sonoko
authors.initials: S
authors.lastname: Kumamoto
authors.forename: Takanori
authors.initials: T
authors.lastname: Shinjo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
keywords: ARB; adipocyte; inflammation; macrophage; type 2 diabetes; valsartan