Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects.
OBJECTIVE
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.


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-alpha 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.


CONCLUSIONS
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.
Itoh
Michiko
M
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.
Suganami
Takayoshi
T
Satoh
Noriko
N
Tanimoto-Koyama
Kanami
K
Yuan
Xunmei
X
Tanaka
Miyako
M
Kawano
Hiroyuki
H
Yano
Takashi
T
Aoe
Seiichiro
S
Takeya
Motohiro
M
Shimatsu
Akira
A
Kuzuya
Hideshi
H
Kamei
Yasutomi
Y
Ogawa
Yoshihiro
Y
D017667:Adipocytes / Q000187:drug effects*; D052242:Adiponectin / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000473:pathology; D000818:Animals; D019440:Anti-Obesity Agents / Q000494:pharmacology*; D018920:Coculture Techniques; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005234:Fatty Liver; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D019440:Anti-Obesity Agents; D014280:Triglycerides; D015118:Eicosapentaenoic Acid