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Current Opinion in Clinical Nutrition & Metabolic Care:
doi: 10.1097/MCO.0b013e32834777fa
Genes and cell metabolism: Edited by Nada Abumrad

The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease

Martínez-Clemente, Marcosa; Clària, Joana,b,c; Titos, Esthera,b

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Purpose of review: Obesity is a major risk factor for metabolic syndrome-related comorbidities such as insulin resistance, type-II diabetes, and nonalcoholic fatty liver disease (NAFLD). A wealth of evidence indicates that the associated pathologies of the metabolic syndrome are aggravated by the presence of a chronic state of ‘low-grade’ inflammation in the adipose tissue. This article discusses recent data implicating lipoxygenases and especially 5-lipoxygenase and its derived products, the leukotrienes, in mounting adipose tissue inflammation and related pathologies in obesity.

Recent findings: Overexpression of selected members of the 5-lipoxygenase pathway and increased leukotriene production are common findings in excessive visceral fat depots. In these conditions, 5-lipoxygenase products exert potent proinflammatory actions including induction of nuclear factor-κB and secretion of proinflammatory and insulin resistant adipokines (i.e., monocyte chemotactic protein-1, tumor necrosis factor-α, macrophage inflammatory protein-1γ, and interleukin-6) by adipose tissue. The 5-lipoxygenase pathway also plays a major role in mounting inflammation in hepatic tissue and has emerged as a pathogenic factor in obesity-induced NAFLD. Similar role in NAFLD has been proposed for the 12/15-lipoxygenase pathway.

Summary: Modulation of lipoxygenases represents a novel target in the prevention of adipose tissue and hepatic dysfunction related to the metabolic syndrome.

© 2011 Lippincott Williams & Wilkins, Inc.


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