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

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

Current Opinion in Clinical Nutrition & Metabolic Care: July 2011 - Volume 14 - Issue 4 - p 347–353
doi: 10.1097/MCO.0b013e32834777fa
Genes and cell metabolism: Edited by Nada Abumrad

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.

aDepartment of Biochemistry and Molecular Genetics, Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, Spain

bCIBERehd, Spain

cDepartment of Physiological Sciences I, University of Barcelona, Barcelona, Spain

Correspondence to Dr Joan Clària, Department of Biochemistry and Molecular Genetics, Hospital Clínic, Villarroel 170, Barcelona 08036, Spain Tel: +34 93 2275 400x2814; fax: +34 93 2275 454; e-mail: jclaria@clinic.ub.es

© 2011 Lippincott Williams & Wilkins, Inc.