Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice.
Osteopontin is required for the early onset of high fat diet-induced insulin resistance in mice.
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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。
DOI：
10.1371/journal.pone.0013959
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发表时间：
2010-11-12
期刊：
影响因子：
3.7
通讯作者：
Sears DD
中科院分区：
文献类型：
--
作者：
Chapman J;Miles PD;Ofrecio JM;Neels JG;Yu JG;Resnik JL;Wilkes J;Talukdar S;Thapar D;Johnson K;Sears DD
胰岛素抵抗表现在肌肉、脂肪组织和肝脏中，并且与脂肪组织炎症相关。调节饮食诱导的胰岛素抵抗发作的细胞成分和机制尚不清楚。我们最初观察到肥胖、胰岛素抵抗的人和大鼠脂肪组织中骨桥蛋白（OPN）mRNA过表达，这两个物种中的噻唑烷二酮（TZD）治疗使其正常化。OPN调节炎症，并与慢性肥胖引起的致病性疾病有关。因此，我们使用2-4周高脂饮食（HFD）模型测试了OPN参与胰岛素抵抗早期发展的假设。喂食HFD 2周的OPN KO小鼠完全免受在野生型（WT）对照中发展的严重骨骼肌、肝脏和脂肪组织胰岛素抵抗的影响，如通过高胰岛素血正葡萄糖钳夹和急性胰岛素刺激研究所确定的。尽管两周HFD未改变任一品系的体重或血浆游离脂肪酸和细胞因子，但HFD诱导的高瘦素血症、脂肪组织炎症（巨噬细胞和细胞因子）增加和脂肪细胞肥大在WT小鼠中显著，在OPN KO小鼠中钝化或不存在。在2周和4周HFD喂养的WT小鼠中，脂肪组织OPN蛋白亚型表达显著改变，但总OPN蛋白不变。OPN KO骨髓基质细胞在体外比WT细胞成骨性更强，成脂性更弱。有趣的是，这两种分化途径在体外WT细胞中受到HFD的相反影响。我们报告的OPN KO表型反映了对胰岛素抵抗的保护作用，这与脂肪细胞生物学和脂肪组织炎症状态的变化有关。OPN是HFD诱导的胰岛素抵抗发展中的关键组分。
Insulin resistance is manifested in muscle, adipose tissue, and liver and is associated with adipose tissue inflammation. The cellular components and mechanisms that regulate the onset of diet-induced insulin resistance are not clearly defined. We initially observed osteopontin (OPN) mRNA over-expression in adipose tissue of obese, insulin resistant humans and rats which was normalized by thiazolidinedione (TZD) treatment in both species. OPN regulates inflammation and is implicated in pathogenic maladies resulting from chronic obesity. Thus, we tested the hypothesis that OPN is involved in the early development of insulin resistance using a 2–4 week high fat diet (HFD) model. OPN KO mice fed HFD for 2 weeks were completely protected from the severe skeletal muscle, liver and adipose tissue insulin resistance that developed in wild type (WT) controls, as determined by hyperinsulinemic euglycemic clamp and acute insulin-stimulation studies. Although two-week HFD did not alter body weight or plasma free fatty acids and cytokines in either strain, HFD-induced hyperleptinemia, increased adipose tissue inflammation (macrophages and cytokines), and adipocyte hypertrophy were significant in WT mice and blunted or absent in OPN KO mice. Adipose tissue OPN protein isoform expression was significantly altered in 2- and 4-week HFD-fed WT mice but total OPN protein was unchanged. OPN KO bone marrow stromal cells were more osteogenic and less adipogenic than WT cells in vitro. Interestingly, the two differentiation pathways were inversely affected by HFD in WT cells in vitro. The OPN KO phenotypes we report reflect protection from insulin resistance that is associated with changes in adipocyte biology and adipose tissue inflammatory status. OPN is a key component in the development of HFD-induced insulin resistance.
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影响因子：
7.7
作者：
Hong EG;Ko HJ;Cho YR;Kim HJ;Ma Z;Yu TY;Friedline RH;Kurt-Jones E;Finberg R;Fischer MA;Granger EL;Norbury CC;Hauschka SD;Philbrick WM;Lee CG;Elias JA;Kim JK
通讯作者：
Kim JK
影响因子：
15.9
作者：
Bruemmer, D;Collins, AR;Hsueh, WA
通讯作者：
Hsueh, WA
影响因子：
5.3
作者：
Kveiborg, M;Sabatakos, G;Baron, R
通讯作者：
Baron, R
影响因子：
5.2
作者：
Chae, Sujin;Jun, Hyoung-Oh;Kim, Kyu-Won
通讯作者：
Kim, Kyu-Won
影响因子：
3.7
作者：
Ishijima, Muneaki;Ezura, Yoichi;Noda, Masaki
通讯作者：
Noda, Masaki