Kim Dong Hee, Cho Yoon Mi, Lee Kyung Hye, Jeong Seong-Whan, Kwon Oh-Joo
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2017 Jul 1;488(3):477-482. doi: 10.1016/j.bbrc.2017.05.066. Epub 2017 May 15.
In obese patients, free fatty acids ectopically accumulated in non-adipose tissues cause cell death. Saturated fatty acids are more deleterious to non-adipose cells, and supplementation with monounsaturated fatty acids has been proposed to rescue cells from saturated fatty acid-induced cytotoxicity; however, the mechanisms are not well understood. To understand the cytoprotective role of monounsaturated fatty acids in lipotoxic cell death of macrophages, we investigated the antagonizing effect of oleate and the underlying mechanisms in palmitate-treated RAW264.7 cells. Palmitate strongly induced apoptosis in macrophages by increasing CD36 expression, which was identified to mediate both endoplasmic reticulum stress and the generation of reactive oxygen species. Co-treatment with oleate significantly reduced CD36 expression and its downstream signaling pathways of apoptosis in palmitate-treated cells. These findings provide a novel mechanism by which oleate protects macrophages from palmitate-induced lipotoxicity.
在肥胖患者中，游离脂肪酸在非脂肪组织中异位蓄积会导致细胞死亡。饱和脂肪酸对非脂肪细胞的危害更大，有人提出补充单不饱和脂肪酸可使细胞免受饱和脂肪酸诱导的细胞毒性作用；然而，其机制尚不清楚。为了解单不饱和脂肪酸在巨噬细胞脂毒性细胞死亡中的细胞保护作用，我们研究了油酸在棕榈酸处理的RAW264.7细胞中的拮抗作用及其潜在机制。棕榈酸通过增加CD36表达强烈诱导巨噬细胞凋亡，已确定CD36介导内质网应激和活性氧的产生。油酸与棕榈酸共同处理可显著降低棕榈酸处理细胞中CD36的表达及其下游凋亡信号通路。这些发现提供了一种新的机制，即油酸可保护巨噬细胞免受棕榈酸诱导的脂毒性。
