Highly Purified Eicosapentaenoic Acid Increases Interleukin-10 Levels of Peripheral Blood Monocytes in Obese Patients With Dyslipidemia
- Noriko Satoh-Asahara, MD, PHD1⇓,
- Akira Shimatsu, MD, PHD1,2,
- Yousuke Sasaki, BSC1,
- Hidenori Nakaoka, PHD1,
- Akihiro Himeno, MD1,
- Mayu Tochiya, MD3,
- Shigeo Kono, MD, PHD1,3,
- Tomohide Takaya, PHD2,
- Koh Ono, MD, PHD4,
- Hiromichi Wada, MD, PHD2,
- Takayoshi Suganami, MD, PHD5,
- Koji Hasegawa, MD, PHD2 and
- Yoshihiro Ogawa, MD, PHD5,6
- 1Division of Diabetic Research, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
- 2Translational Research, Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
- 3Diabetes Center, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
- 4Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- 5Department of Molecular Medicine and Metabolism, Medical Research Institute, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- 6Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Corresponding author: Noriko Satoh-Asahara, .
OBJECTIVE It has recently been highlighted that proinflammatory (M1) macrophages predominate over anti-inflammatory (M2) macrophages in obesity, thereby contributing to obesity-induced adipose inflammation and insulin resistance. A recent clinical trial revealed that highly purified eicosapentaenoic acid (EPA) reduces the incidence of major coronary events. In this study, we examined the effect of EPA on M1/M2-like phenotypes of peripheral blood monocytes in obese dyslipidemic patients.
RESEARCH DESIGN AND METHODS Peripheral blood monocytes were prepared from 26 obese patients without and 90 obese patients with dyslipidemia. Of the latter 90 obese patients with dyslipidemia, 82 patients were treated with or without EPA treatment (1.8 g daily) for 3 months.
RESULTS Monocytes in obese patients with dyslipidemia showed a significantly lower expression of interleukin-10 (IL-10), an M2 marker, than those without dyslipidemia. EPA significantly increased serum IL-10 and EPA levels, the EPA/arachidonic acid (AA) ratio, and monocyte IL-10 expression and decreased the pulse wave velocity (PWV), an index of arterial stiffness, compared with the control group. After EPA treatment, the serum EPA/AA ratio was significantly correlated with monocyte IL-10 expression. Only increases in monocyte IL-10 expression and serum adiponectin were independent determinants of a decreased PWV by EPA. Furthermore, EPA significantly increased the expression and secretion of IL-10 in human monocytic THP-1 cells through a peroxisome proliferator–activated receptor (PPAR)γ-dependent pathway.
CONCLUSIONS This study is the first to show that EPA increases the monocyte IL-10 expression in parallel with decrease of arterial stiffness, which may contribute to the antiatherogenic effect of EPA in obese dyslipidemic patients.
Clinical trial reg. no. UMIN 000000559, www.umin.ac.jp/ctr/.
This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-0269/-/DC1.
- Received February 8, 2012.
- Accepted June 14, 2012.
- © 2012 by the American Diabetes Association.
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