12- and 15-lipoxygenases in adipose tissue inflammation

The lipoxygenases (LOs) are principal enzymes involved in the oxidative metabolism of polyunsaturated fatty acids, including arachidonic acid. 12- and 15-LO and their lipid metabolites have been implicated in the development of insulin resistance and diabetes. Adipose tissue, and in particular visceral adipose tissue, plays a primary role in the development of the inflammation seen in these conditions. 12- and 15-LO and their lipid metabolites act as upstream regulators of many of the cytokines involved in the inflammatory response in adipose tissue. While the role that 12- and 15-LO play in chronically inflamed adipose tissue is becoming clearer, there are still many questions that remain unanswered regarding their activation, signaling pathways, and roles in healthy fat. 12- and 15-LO also generate products with anti-inflammatory properties that are under investigation. Therefore, 12- and 15-LO have the potential to be very important targets for therapeutics aimed at reducing insulin resistance and the comorbid conditions associated with obesity.

► 12- and 15-lipoxygenases are expressed in many tissues, including adipose tissue. ► 12- and 15-lipoxygenases can generate pro- and anti-inflammatory metabolites. ► 12-Lipoxygenase activity in adipocytes is required for adipocyte differentiation. ► 12- and 15-lipoxygenases in obesity promote the onset of metabolic dysfunction. ► Therapeutics against 12- and 15-lipoxygenases may treat metabolic dysfunction.