Adipose Tissue-Specific Deletion of 12/15-Lipoxygenase Protects Mice from the Consequences of a High-Fat Diet

• Published in: Mediators of Inflammation 2012-01, Vol.2012 (2012), p.759-771-184
• Main Authors: Leone, Kendall A., Grzesik, Wojciech J., Morris, Margaret A., Cole, Banumathi K., Nadler, Jerry L.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - enzymology; Animals; Arachidonate 12-Lipoxygenase - deficiency; Arachidonate 12-Lipoxygenase - genetics; Arachidonate 12-Lipoxygenase - physiology; Arachidonate 15-Lipoxygenase - deficiency; Arachidonate 15-Lipoxygenase - genetics; Arachidonate 15-Lipoxygenase - physiology; Diet, High-Fat - adverse effects; Glucose - metabolism; Inflammation - prevention & control; Insulin-Secreting Cells - physiology; Lipids - blood; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2012/851798

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-LOloxP/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.