| Autor: |
Song MY; Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea., Kim SH; Department of Surgery, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea., Ryoo GH; Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea., Kim MK; Research Institute of Dong-A ST Co. Ltd., Yongin, Gyeonggi, 17073, Republic of Korea., Cha HN; Department of Physiology, College of Medicine, Yeungnam University, Daegu, 42415, Republic of Korea., Park SY; Department of Physiology, College of Medicine, Yeungnam University, Daegu, 42415, Republic of Korea., Hwang HP; Department of Surgery, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea., Yu HC; Department of Surgery, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea., Bae EJ; College of Pharmacy, Woosuk University, Wanju, Jeonbuk, 55338, Republic of Korea. ejbae@woosuk.ac.kr., Park BH; Department of Biochemistry and Molecular Biology, Chonbuk National University Medical School, Jeonju, Jeonbuk, 54896, Republic of Korea. bhpark@jbnu.ac.kr. |
| Abstrakt: |
Adipose tissue inflammation is a reproducible feature of obesity and obesity-linked insulin resistance. Although sirtuin 6 (Sirt6) deficiency has previously been implicated in diet-induced obesity and systemic insulin resistance, the adipocyte-specific role of Sirt6 in the regulation of adipose tissue inflammation and systemic metabolic dysfunction in mice fed normal chow and in humans remains elusive. Here, using Adipoq-Cre-mediated adipocyte-specific Sirt6 knockout (aS6KO) mice, we explored whether adipocyte Sirt6 inhibits adipose tissue inflammation and its underlying mechanism. aS6KO mice fed normal chow gained more body weight and fat mass than wild-type mice and exhibited glucose intolerance and systemic insulin resistance. Measurement of plasma and tissue cytokines and flow cytometric analysis of adipose stromal vascular cells indicated a decrease in alternatively activated M2 macrophages in the adipose tissue of aS6KO mice. Mechanistically, Sirt6 regulated the expression of the canonical type 2 cytokine IL-4 by adipocytes in a cell autonomous manner, which in turn affects M2 macrophage polarization. Consistent with animal experimental data, the degree of obesity and insulin resistance demonstrated by the body mass index, fasting blood glucose and HbA1c correlated negatively with the expression of Sirt6 in human visceral fat tissues. Collectively, these results suggest that adipocyte Sirt6 regulates body weight gain and insulin sensitivity independent of diet, and the increased IL-4 production by Sirt6 and resultant M2 polarization of adipose tissue macrophages may attenuate proinflammatory responses in adipose tissue. |
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