decrease of mir-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin减少mir - 146 b - 5 - p在肥胖与单核细胞丧失脂联素的抗炎但不是胰岛素信号传导作用.pdfVIP

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decrease of mir-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin减少mir - 146 b - 5 - p在肥胖与单核细胞丧失脂联素的抗炎但不是胰岛素信号传导作用.pdf

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decrease of mir-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin减少mir - 146 b - 5 - p在肥胖与单核细胞丧失脂联素的抗炎但不是胰岛素信号传导作用

Decrease of miR-146b-5p in Monocytes during Obesity Is Associated with Loss of the Anti-Inflammatory but Not Insulin Signaling Action of Adiponectin 1 1 2 1 Maarten Hulsmans , Els Van Dooren , Chantal Mathieu , Paul Holvoet * 1 Atherosclerosis and Metabolism Unit, Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium, 2 Clinical and Experimental Endocrinology Unit, Department of Clinical and Experimental Medicine, KU Leuven, Leuven, Belgium Abstract Background: Low adiponectin, a well-recognized antidiabetic adipokine, has been associated with obesity-related inflammation, oxidative stress and insulin resistance. Globular adiponectin is an important regulator of the interleukin-1 receptor-associated kinase (IRAK)/NFkB pathway in monocytes of obese subjects. It protects against inflammation and oxidative stress by inducing IRAK3. microRNA (miR)-146b-5p inhibits NFkB-mediated inflammation by targeted repression of IRAK1 and TNF receptor-associated factor-6 (TRAF6). Therefore, we measured the expression of miR-146b-5p in monocytes of obese subjects. Because it was low we determined the involvement of this miR in the anti-inflammatory, antioxidative and insulin signaling action of globular adiponectin. Methods: miR-146b-5p expression in monocytes of obese subjects was determined by qRT-PCR. The effect of miR-146b-5p silencing on molecular markers of inflammation, oxidative stress and insulin signaling and the association with globular adiponectin was assessed in human THP-1 monocytes. Results: miR-146b-5p was downregulated in monocytes of obese persons. Low globular adiponectin decreased miR-146b- 5p and IRAK3 in THP-1 monocytes, associated with increased mitochondrial reactive oxygen specie