Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia.
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.


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.
Division of Diabetic Research, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan. norikos@oregano.ocn.ne.jp
Noriko
N
Satoh-Asahara
Akira
A
Shimatsu
Yousuke
Y
Sasaki
Hidenori
H
Nakaoka
Akihiro
A
Himeno
Mayu
M
Tochiya
Shigeo
S
Kono
Tomohide
T
Takaya
Koh
K
Ono
Hiromichi
H
Wada
Takayoshi
T
Suganami
Koji
K
Hasegawa
Yoshihiro
Y
Ogawa
D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*
D016753:Interleukin-10; D015118:Eicosapentaenoic Acid