Document Detail


Impaired local production of proresolving lipid mediators in obesity and 17-HDHA as a potential treatment for obesity-associated inflammation.
MedLine Citation:
PMID:  23349501     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity-induced chronic low-grade inflammation originates from adipose tissue and is crucial for obesity-driven metabolic deterioration, including insulin resistance and type 2 diabetes. Chronic inflammation may be a consequence of a failure to actively resolve inflammation and could result from a lack of local specialized proresolving lipid mediators (SPMs), such as resolvins and protectins, which derive from the n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We assessed obesity-induced changes of n-3-derived SPMs in adipose tissue and the effects of dietary EPA/DHA thereon. Moreover, we treated obese mice with SPM precursors and investigated the effects on inflammation and metabolic dysregulation. Obesity significantly decreased DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA, resolvin D1 precursor) and protectin D1 (PD1) levels in murine adipose tissue. Dietary EPA/DHA treatment restored endogenous biosynthesis of n-3-derived lipid mediators in obesity while attenuating adipose tissue inflammation and improving insulin sensitivity. Notably, 17-HDHA treatment reduced adipose tissue expression of inflammatory cytokines, increased adiponectin expression, and improved glucose tolerance parallel to insulin sensitivity in obese mice. These findings indicate that impaired biosynthesis of certain SPM and SPM precursors, including 17-HDHA and PD1, contributes to adipose tissue inflammation in obesity and suggest 17-HDHA as a novel treatment option for obesity-associated complications.
Authors:
Angelika Neuhofer; Maximilian Zeyda; Daniel Mascher; Bianca K Itariu; Incoronata Murano; Lukas Leitner; Eva E Hochbrugger; Peter Fraisl; Saverio Cinti; Charles N Serhan; Thomas M Stulnig
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-24
Journal Detail:
Title:  Diabetes     Volume:  62     ISSN:  1939-327X     ISO Abbreviation:  Diabetes     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-24     Completed Date:  2013-08-02     Revised Date:  2013-11-13    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1945-56     Citation Subset:  AIM; IM    
Affiliation:
Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / metabolism
Animals
Blotting, Western
Docosahexaenoic Acids / metabolism,  therapeutic use*
Eicosapentaenoic Acid / therapeutic use
Flow Cytometry
Humans
Immunohistochemistry
Inflammation / drug therapy*,  immunology*
Male
Mice
Mice, Inbred C57BL
Obesity / drug therapy*,  immunology*,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
P01 GM095467/GM/NIGMS NIH HHS; P01-GM095467/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/protectin D1; 1553-41-9/Eicosapentaenoic Acid; 25167-62-8/Docosahexaenoic Acids; 90780-52-2/17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid

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


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