CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance.
CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance.
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DOI：
10.1371/journal.pone.0058417
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Jetten AM
中科院分区：
文献类型：
--
作者：
Kang HS;Liao G;DeGraff LM;Gerrish K;Bortner CD;Garantziotis S;Jetten AM
CD44 是一种多功能膜受体，参与多种生物过程的调节，包括炎症。肥胖期间肝脏和白色脂肪组织 (WAT) 中的 CD44 表达升高，表明 CD44 在代谢综合征中可能具有调节作用。为了研究这一假设，我们使用 CD44 缺失小鼠检查了 CD44 表达缺失对代谢综合征各种特征发展的影响。我们的研究表明，CD44 缺陷小鼠 (CD44KO) 对高脂饮食 (HFD) 诱导的肝脂肪变性、WAT 相关炎症和胰岛素抵抗的易感性显着降低。参与脂肪酸合成和运输（Fasn和Cd36）、甘油三酯从头合成（Mogat1）和甘油三酯积累（Cidea、Cidec）的基因表达减少似乎是CD44KO（HFD）小鼠肝脏脂质积累减少的部分原因。此外，CD44KO(HFD)肝脏中各种炎症和细胞基质基因的表达大大减少，包括几种趋化因子及其受体、骨桥蛋白以及几种基质金属蛋白酶和胶原基因，这与炎症和纤维形成的减少一致。相比之下，CD44KO(HFD) WAT中的脂质积累显着增加，而与WT(HFD)小鼠相比，CD44KO(HFD)小鼠WAT中巨噬细胞浸润和巨噬细胞标记基因表达减少所表明的炎症显着减少。 CD44KO(HFD)小鼠比WT(HFD)小鼠仍然具有更高的胰岛素敏感性和葡萄糖耐受性，并且表现出较低的血液胰岛素水平。我们的研究表明，CD44 在调节代谢综合征的多个方面发挥着关键作用，并可能为胰岛素抵抗的管理提供新的治疗靶点。
CD44 is a multifunctional membrane receptor implicated in the regulation of several biological processes, including inflammation. CD44 expression is elevated in liver and white adipose tissue (WAT) during obesity suggesting a possible regulatory role for CD44 in metabolic syndrome. To study this hypothesis, we examined the effect of the loss of CD44 expression on the development of various features of metabolic syndrome using CD44 null mice. Our study demonstrates that CD44-deficient mice (CD44KO) exhibit a significantly reduced susceptibility to the development of high fat-diet (HFD)-induced hepatic steatosis, WAT-associated inflammation, and insulin resistance. The decreased expression of genes involved in fatty acid synthesis and transport (Fasn and Cd36), de novo triglyceride synthesis (Mogat1), and triglyceride accumulation (Cidea, Cidec) appears in part responsible for the reduced hepatic lipid accumulation in CD44KO(HFD) mice. In addition, the expression of various inflammatory and cell matrix genes, including several chemokines and its receptors, osteopontin, and several matrix metalloproteinases and collagen genes was greatly diminished in CD44KO(HFD) liver consistent with reduced inflammation and fibrogenesis. In contrast, lipid accumulation was significantly increased in CD44KO(HFD) WAT, whereas inflammation as indicated by the reduced infiltration of macrophages and expression of macrophage marker genes, was significantly diminished in WAT of CD44KO(HFD) mice compared to WT(HFD) mice. CD44KO(HFD) mice remained considerably more insulin sensitive and glucose tolerant than WT(HFD) mice and exhibited lower blood insulin levels. Our study indicates that CD44 plays a critical role in regulating several aspects of metabolic syndrome and may provide a new therapeutic target in the management of insulin resistance.
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骨桥蛋白是高脂肪饮食诱导的小鼠胰岛素抵抗早期发生所必需的。
影响因子：
3.7
作者：
Chapman J;Miles PD;Ofrecio JM;Neels JG;Yu JG;Resnik JL;Wilkes J;Talukdar S;Thapar D;Johnson K;Sears DD
通讯作者：
Sears DD
影响因子：
33.6
作者：
Jiang D;Liang J;Noble PW
通讯作者：
Noble PW
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
DOI：
10.1161/atvbaha.111.241927
发表时间：
2012-08-01
影响因子：
8.7
作者：
Hursting, Stephen D.;Hursting, Marcie J.
通讯作者：
Hursting, Marcie J.
影响因子：
4.6
作者：
Kang, Hong Soon;Okamoto, Kyoko;Jetten, Anton M.
通讯作者：
Jetten, Anton M.