Document Detail


Differential expression and localization of 12/15 lipoxygenases in adipose tissue in human obese subjects.
MedLine Citation:
PMID:  21094135     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adipose tissue inflammation in obesity is a major factor leading to cardiovascular disease and type 2 diabetes.12/15 lipoxygenases (ALOX) play an important role in the generation of inflammatory mediators, insulin resistance and downstream immune activation in animal models of obesity. However, the expression and roles of 12/15ALOX isoforms, and their cellular sources in human subcutaneous (sc) and omental (om) fat in obesity is unknown. The objective of this study was to examine the gene expression and localization of ALOX isoforms and relevant downstream cytokines in subcutaneous (sc) and omental (om) adipose tissue in obese humans. Paired biopsies of sc and om fat were obtained during bariatric surgeries from 24 morbidly obese patients. Gene and protein expression for ALOX15a, ALOX15b and ALOX 12 were measured by real-time PCR and western blotting in adipocytes and stromal vascular fractions (SVF) from om and sc adipose tissue along with the mRNA expression of the downstream cytokines IL-12a, IL-12b, IL-6, IFNγ and the chemokine CXCL10. In a paired analysis, all ALOX isoforms, IL-6, IL-12a and CXCL10 were significantly higher in om vs. sc fat. ALOX15a mRNA and protein expression was found exclusively in om fat. All of the ALOX isoforms were expressed solely in the SVF. Further fractionation of the SVF in CD34+ and CD34- cells indicated that ALOX15a is predominantly expressed in the CD34+ fraction including vascular and progenitor cells, while ALOX15B is mostly expressed in the CD34- cells containing various leucocytes and myeloid cells. This result was confirmed by immunohistochemistry showing exclusive localization of ALOX15a in the om fat and predominantly in the vasculature and non-adipocyte cells. Our finding is identifying selective expression of ALOX15a in human om but not sc fat. This is a study showing a major inflammatory gene exclusively expressed in visceral fat in humans.
Authors:
Anca D Dobrian; David C Lieb; Qian Ma; John W Lindsay; Banumathi K Cole; Kaiwen Ma; Swarup K Chakrabarti; Norine S Kuhn; Stephen D Wohlgemuth; Mark Fontana; Jerry L Nadler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-11-19
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  403     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-20     Completed Date:  2011-01-20     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  485-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / enzymology*
Adult
Arachidonate 12-Lipoxygenase / genetics,  metabolism*
Arachidonate 15-Lipoxygenase / genetics,  metabolism*
Cytokines / metabolism
Female
Humans
Isoenzymes / genetics,  metabolism
Male
Middle Aged
Obesity / enzymology*
Grant Support
ID/Acronym/Agency:
P01 HL055798/HL/NHLBI NIH HHS; P01 HL055798-09/HL/NHLBI NIH HHS; P01 HL55798/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/12-15-lipoxygenase; 0/Cytokines; 0/Isoenzymes; EC 1.13.11.31/Arachidonate 12-Lipoxygenase; EC 1.13.11.33/Arachidonate 15-Lipoxygenase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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