title: The 5-lipoxygenase/leukotriene pathway in obesity, insulin resistance, and fatty liver disease.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Modulation of lipoxygenases represents a novel target in the prevention of adipose tissue and hepatic dysfunction related to the metabolic syndrome.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Hospital Clínic, Centre Esther Koplowitz, IDIBAPS, CIBERehd, and Department of Physiological Sciences I, University of Barcelona, Barcelona, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Martínez-Clemente
authors.forename: Joan
authors.initials: J
authors.lastname: Clària
authors.forename: Esther
authors.initials: E
authors.lastname: Titos
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005234:Fatty Liver / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D015289:Leukotrienes / Q000235:genetics / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D024821:Metabolic Syndrome / Q000209:etiology; D016328:NF-kappa B / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D012307:Risk Factors; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C475064:12-15-lipoxygenase; D054392:Adipokines; D018932:Chemokine CCL2; D007328:Insulin; D015850:Interleukin-6; D015289:Leukotrienes; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D001094:Arachidonate 5-Lipoxygenase