Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.
Adiponectin induces A20 expression in adipose tissue to confer metabolic benefit.
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作者：
Hand LE;Usan P;Cooper GJ;Xu LY;Ammori B;Cunningham PS;Aghamohammadzadeh R;Soran H;Greenstein A;Loudon AS;Bechtold DA;Ray DW
肥胖是代谢性疾病的主要风险因素，白色脂肪组织(WAT)炎症是一种关键的潜在病理。我们详细说明，缺乏混响α的小鼠表现出脂肪储存的增加，而不会出现预期的WAT炎症增加或胰岛素敏感性丧失。与大多数肥胖动物模型和肥胖的人类患者不同，Reverbα−/−小鼠在体外表现出血清脂联素水平升高和WAT外植体分泌脂联素增加，这突显了这种脂肪因子在肥大性WAT中的潜在抗炎作用。事实上，脂联素被发现可以抑制原代巨噬细胞对内毒素和促炎性脂肪酸的反应，这种抑制依赖于糖原合成酶激酶3β的激活和A20的诱导。混响α−/−水池中减弱的炎症反应与A20蛋白的紧张性升高有关，体外显示依赖于A20。我们还证明肥胖受试者中脂肪A20的表达与胰岛素敏感性指标呈负相关。此外，减肥手术导致的体重减轻伴随着Wat A20表达的增强，这与血清脂联素的升高以及包括C反应蛋白在内的代谢和炎症标志物的改善呈正相关。这些发现确定A20是WAT中脂联素抗炎作用的媒介，并且是减轻肥胖相关病理的潜在靶点。
Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverbα exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverbα−/− mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3β activation and induction of A20. Attenuated inflammatory responses in Reverbα−/− WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery–induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
29
作者：
Baker RG;Hayden MS;Ghosh S
通讯作者：
Ghosh S
DOI：
10.1073/pnas.1106750109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Gibbs, Julie E.;Blaikley, John;Loudon, Andrew S. I.
通讯作者：
Loudon, Andrew S. I.
影响因子：
82.9
作者：
Maeda, N;Shimomura, I;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
8.2
作者：
Scheer, F. A. J. L.;Chan, J. L.;Fargnoli, J.;Chamberland, J.;Arampatzi, K.;Shea, S. A.;Blackburn, G. L.;Mantzoros, C. S.
通讯作者：
Mantzoros, C. S.