12-lipoxygenase promotes obesity-induced oxidative stress in pancreatic islets

摘要: High-fat diets lead to obesity, inflammation, and dysglycemia. 12-Lipoxygenase (12-LO) is activated by high-fat catalyzes the oxygenation of cellular arachidonic acid form proinflammatory intermediates. We hypothesized that 12-LO in pancreatic islet sufficient cause dysglycemia setting feeding. To test this, we generated pancreas-specific knockout mice studied their metabolic molecular adaptations diets. Whereas control littermates displayed identical weight gain, body fat distribution, macrophage infiltration into fat, exhibited greater adaptive hyperplasia, improved insulin secretion, complete protection from At level, deletion resulted increases antioxidant enzymes Sod1 Gpx1 response The absence or inhibition led nuclear Nrf2, a transcription factor responsible for activation genes encoding enzymes. Our data reveal novel pathway which suppresses prevents responses