title: Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of 3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages.
abstract: Macrophages in adipose tissue reportedly play a major role in the development of insulin resistance and chronic inflammation associated with obesity. On the other hand, several clinical trials have revealed angiotensin II receptor blockers (ARBs) to improve insulin resistance. In this study, we analyzed the gene expression profile of 3T3-L1 adipocytes co-cultured with LPS-treated RAW264.7 macrophages in the presence or the absence of the angiotensin receptor 1 blocker valsartan, for 4, 8, 12 and 24 h. The genes of which expressions were affected by LPS-treated RAW macrophages but normalized by co-addition of valsartan were analyzed using KeyMolnet Lite. They included many NF-κB, thyroid receptor and AP-1 target transcripts. In addition, the expression patterns of caspases, integrins, matrix metallopeptidases and adipogenic genes, altered by co-culture with LPS-treated RAW cells, were generally normalized by valsartan treatment. 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, apoptosis and fibrotic changes of adipose tissue. Although there may be multiple mechanisms by which ARBs ameliorate insulin resistance, for example, through effects on muscle or other tissues via the circulatory system, this is the first report demonstrating that a favorable effect of valsartan involves normalization of the interaction between adipocytes and macrophages. This mechanism of valsartan action holds promise for developing treatments for obesity-related insulin resistance.:
authors: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Sonoko
authors: S
authors: Kumamoto
authors: Department of Endocrinology and Metabolism, Institute for Adult Disease, Asahi Life Foundation, Japan.
authors: Akifumi
authors: A
authors: Kushiyama
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Yusuke
authors: Y
authors: Nakatsu
authors: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
authors: Hideyuki
authors: H
authors: Sakoda
authors: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
authors: Midori
authors: M
authors: Fujishiro
authors: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Misaki
authors: M
authors: Iwashita
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Haruya
authors: H
authors: Ohno
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Jun
authors: J
authors: Zhang
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Ying
authors: Y
authors: Guo
authors: Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, University of Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Aburatani
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Hideaki
authors: H
authors: Kamata
authors: Department of Dental Science for Health Promotion, Division of Cervico-Gnathostomatology, Graduate School of Biomedical Sciences, Hiroshima University, Japan.
authors: Fusanori
authors: F
authors: Nishimura
authors: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Japan. Electronic address:tasano@hiroshima-u.ac.jp.
authors: Tomoichiro
authors: T
authors: Asano