title: Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet.
abstract: 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.
authors: Department of Internal Medicine, Strelitz Diabetes Center, Eastern Virginia Medical School, Norfolk, VA 23507, USA. colebk@evms.edu
authors: Banumathi K
authors: BK
authors: Cole
authors: Margaret A
authors: MA
authors: Morris
authors: Wojciech J
authors: WJ
authors: Grzesik
authors: Kendall A
authors: KA
authors: Leone
authors: Jerry L
authors: JL
authors: Nadler
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001093:Arachidonate 15-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000517:prevention & control; D050417:Insulin-Secreting Cells / Q000502:physiology; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D008055:Lipids; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D005947:Glucose