title: Adipose tissue 12/15 lipoxygenase pathway in human obesity and diabetes.
abstract: BACKGROUND
  Visceral adipose tissue (VAT) is a key contributor to chronic inflammation in obesity. The 12/15-lipoxygenase pathway (ALOX) is present in adipose tissue (AT) and leads to inflammatory cascades that are causal for the onset of insulin resistance in rodent models of obesity.
  
  
  OBJECTIVE
  The pathophysiology of the ALOX 12/15 pathway in human AT is unknown. We characterized the ALOX pathway in different AT depots in obese humans with or without type 2 diabetes (T2D).
  
  
  METHODS
  This study includes a cross-sectional cohort of 46 morbidly obese (body mass index >39 kg/m(2)) nondiabetic (n = 25) and T2D (n = 21) subjects.
  
  
  METHODS
  This study was conducted at Eastern Virginia Medical School (Norfolk, Virginia) in collaboration with Sentara Metabolic and Weight Loss Surgery Center (Sentara Medical Group, Norfolk, Virginia).
  
  
  METHODS
  Twenty-five obese (body mass index 44.8 ± 4.4 kg/m(2)) nondiabetic (hemoglobin A1c 5.83% ± 0.27%) and 21 obese (43.4 ± 4.1 kg/m(2)) and T2D (hemoglobin A1c 7.66% ± 1.22%) subjects were included in the study. The subjects were age matched and both groups had a bias toward female gender.
  
  
  METHODS
  Expression of ALOX isoforms along with fatty acid substrates and downstream lipid metabolites were measured. Correlations with depot-specific inflammatory markers were also established.
  
  
  RESULTS
  ALOX 12 expression and its metabolite 12(S)-hydroxyeicosatetraenoic acid were significantly increased in the VAT of T2D subjects. ALOX 15A was exclusively expressed in VAT in both groups. ALOX 12 expression positively correlated with expression of inflammatory genes IL-6, IL-12a, CXCL10, and lipocalin-2.
  
  
  CONCLUSIONS
  ALOX 12 may have a critical role in regulation of inflammation in VAT in obesity and T2D. Selective ALOX 12 inhibitors may constitute a new approach to limit AT inflammation in human obesity.
authors: Departments of Internal Medicine (D.C.L., B.K.C., J.L.N.) and Physiological Sciences (J.J.B., M.A.H., M.S.A., B.A.H., A.D.D.) and Graduate Program in Public Health (H.B.), Eastern Virginia Medical School, Norfolk, Virginia 23507; and Sentara Metabolic and Weight Loss Surgery Center (S.D.W., M.A.F.), Sentara Medical Group, Norfolk, Virginia 23502.
authors: David C
authors: DC
authors: Lieb
authors: Joshua J
authors: JJ
authors: Brotman
authors: Margaret A
authors: MA
authors: Hatcher
authors: Myo S
authors: MS
authors: Aye
authors: Banumathi K
authors: BK
authors: Cole
authors: Bronson A
authors: BA
authors: Haynes
authors: Stephen D
authors: SD
authors: Wohlgemuth
authors: Mark A
authors: MA
authors: Fontana
authors: Hind
authors: H
authors: Beydoun
authors: Jerry L
authors: JL
authors: Nadler
authors: Anca D
authors: AD
authors: Dobrian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D050152:Intra-Abdominal Fat / Q000201:enzymology* / Q000276:immunology; D050356:Lipid Metabolism / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D015415:Biomarkers; D005227:Fatty Acids; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human; C476558:ALOX12 protein, human; C515716:ALOX15 protein, human