on June 20, 2007
Published online before print June 14, 2007, doi: 10.1161/ATVBAHA.106.136853
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Submitted on November 25, 2006
Accepted on May 9, 2007
Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects
Michiko Itoh ;
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.
* To whom correspondence should be addressed. E-mail: ogawa.mmm{at}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.
Key words: adipocytes • adiponectin • EPA • macrophages • obesity
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