Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet.
Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet.
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DOI：
10.1155/2012/851798
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发表时间：
2012
影响因子：
4.6
通讯作者：
Nadler JL
中科院分区：
文献类型：
--
作者：
Cole BK;Morris MA;Grzesik WJ;Leone KA;Nadler JL
2型糖尿病与肥胖、胰岛素抵抗和脂肪组织炎症有关。12/15-脂氧合酶（12/15-LO）产生促炎脂质介质，其诱导脂肪组织中的炎症。因此，我们研究了小鼠白色脂肪组织中12/15-LO活性在促进肥胖诱导的局部和全身炎症后果中的作用。我们产生了脂肪特异性缺失12/15-LO，aP 2-Cre; 12/15-LO loxP/loxP的小鼠模型，我们称之为ad-12/15-LO小鼠，并将野生型对照和ad-12/15-LO小鼠置于高脂饮食16周，并检查肥胖诱导的炎症和胰岛素抵抗。与野生型小鼠相比，高脂饮食喂养的ad-12/15-LO表现出改善的空腹葡萄糖水平和葡萄糖代谢，并且来自这些小鼠的附睾脂肪组织表现出减少的炎症和巨噬细胞浸润。此外，与野生型小鼠相比，脂肪特异性缺失12/15-LO导致外周胰岛炎症减少，胰岛增大。这些结果表明，在脂肪组织中的12/15-LO表达和胰岛中的炎症之间存在有趣的串扰。因此，脂肪组织中12/15-LO的缺失可以提供局部和全身保护，以避免肥胖诱导的后果，并且阻断脂肪组织中12/15-LO的活性可能是治疗2型糖尿病的新的治疗靶点。
Type 2 diabetes is associated with obesity, insulin resistance, and inflammation in adipose tissue. 12/15-Lipoxygenase (12/15-LO) generates proinflammatory lipid mediators, which induce inflammation in adipose tissue. Therefore we investigated the role of 12/15-LO activity in mouse white adipose tissue in promoting obesity-induced local and systemic inflammatory consequences. We generated a mouse model for fat-specific deletion of 12/15-LO, aP2-Cre; 12/15-LO loxP/loxP, which we call ad-12/15-LO mice, and placed wild-type controls and ad-12/15-LO mice on a high-fat diet for 16 weeks and examined obesity-induced inflammation and insulin resistance. High-fat diet-fed ad-12/15-LO exhibited improved fasting glucose levels and glucose metabolism, and epididymal adipose tissue from these mice exhibited reduced inflammation and macrophage infiltration compared to wild-type mice. Furthermore, fat-specific deletion of 12/15-LO led to decreased peripheral pancreatic islet inflammation with enlarged pancreatic islets when mice were fed the high-fat diet compared to wild-type mice. These results suggest an interesting crosstalk between 12/15-LO expression in adipose tissue and inflammation in pancreatic islets. Therefore, deletion of 12/15-LO in adipose tissue can offer local and systemic protection from obesity-induced consequences, and blocking 12/15-LO activity in adipose tissue may be a novel therapeutic target in the treatment of type 2 diabetes.
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影响因子：
13.6
作者：
Dobrian, Anca D.;Lieb, David C.;Cole, Banumathi K.;Taylor-Fishwick, David A.;Chakrabarti, Swarup K.;Nadler, Jerry L.
通讯作者：
Nadler, Jerry L.
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：
7.7
作者：
Inouye, Karen E.;Shi, Hang;Flier, Jeffrey S.
通讯作者：
Flier, Jeffrey S.
DOI：
10.1152/ajpendo.00373.2011
发表时间：
2012-03-01
影响因子：
5.1
作者：
Cole, Banumathi K.;Kuhn, Norine S.;Chakrabarti, Swarup K.
通讯作者：
Chakrabarti, Swarup K.
影响因子：
4.8
作者：
Fischer-Posovszky, Pamela;Wang, Qiong A.;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.