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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1918.)
© 2007 American Heart Association, Inc.

Vascular Biology

Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects

Michiko Itoh; Takayoshi Suganami; Noriko Satoh; Kanami Tanimoto-Koyama; Xunmei Yuan; Miyako Tanaka; Hiroyuki Kawano; Takashi Yano; Seiichiro Aoe; Motohiro Takeya; Akira Shimatsu; Hideshi Kuzuya; Yasutomi Kamei; Yoshihiro Ogawa

From the Department of Molecular Medicine and Metabolism (M.I., T.S., K.T.-K., X.Y., M.T., Y.K., Y.O.) and the Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstitution of Tooth and Bone (M.T., Y.O.), Medical Research Institute, Tokyo Medical and Dental University; the Clinical Research Institute for Endocrine Metabolic Disease (N.S., A.S.) and Diabetes Center (H.K.), National Hospital Organization, Kyoto Medical Center; the Development Research Pharmaceutical Research Center (H.K., T.Y.), Mochida Pharmaceutical Co Ltd, Shizuoka; the Department of Home Economics (S.A.), Otsuma Women’s University, Tokyo; and the Department of Cell Pathology (M.T.), Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Correspondence to Yoshihiro Ogawa or Takayoshi Suganami, Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. E-mail ogawa.mmm{at}mri.tmd.ac.jp or suganami.mmm@mri.tmd.ac.jp

Objectives— Fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) or n-3 PUFAs have been shown to reduce the incidence of coronary heart disease. Here we investigated the effect of highly purified eicosapentaenoic acid (EPA) on production of adiponectin, the only established antiatherogenic and antiinflammatory adipocytokine, in rodent models of obesity and human obese subjects.

Methods and Results— We demonstrated that EPA increases adiponectin secretion in genetically obese ob/ob mice and high-fat diet–induced obese mice. In the in vitro coculture of adipocytes and macrophages, EPA reversed the coculture-induced decrease in adiponectin secretion at least in part through downregulation of tumor necrosis factor- in macrophages. We also showed significant increase in plasma adiponectin concentrations in human obese subjects after a 3-month treatment with EPA (1.8 g daily). Multivariate regression analysis revealed that EPA treatment is the only independent determinant of plasma adiponectin concentrations.

Conclusion— This study demonstrates that EPA increases adiponectin secretion in rodent models of obesity and human obese subjects, possibly through the improvement of the inflammatory changes in obese adipose tissue. Because EPA has reduced the risk of major coronary events in a large-scale, prospective, randomized clinical trial, this study provides important insight into its therapeutic implication in obesity-related metabolic sequelae.

Here we show that highly purified EPA, the only class of n-3 PUFAs used clinically to treat hyperlipidemia, increases adiponectin secretion in rodent models of obesity and human obese subjects possibly through the improvement of adipose tissue inflammation, thereby providing important insight into its therapeutic implication in obesity-related metabolic sequelae.

Key Words: adipocytes • adiponectin • EPA • macrophages • obesity