Document Detail


Obesity-related alterations in cardiac lipid profile and nondipping blood pressure pattern during transition to diastolic dysfunction in male db/db mice.
MedLine Citation:
PMID:  23142808     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Obesity and a nondipping circadian blood pressure (BP) pattern are associated with diastolic dysfunction. Ectopic lipid accumulation is increasingly recognized as an important metabolic abnormality contributing to diastolic dysfunction. However, little is known about the contribution of different lipids and the composition of lipid analytes to diastolic dysfunction. We have performed functional and structural studies and analyzed cardiac lipid profile at two time points during progression to diastolic dysfunction in a genetic model of obesity. Serial cardiac magnetic resonance imaging and telemetric measures of BP between 12 and 15 wk of age in obese male db/db mice indicated a nondipping circadian BP pattern and normal diastolic function at 12 wk that progressed to a deteriorating nondipping pattern and onset of diastolic dysfunction at 15 wk of age. Lipidomic analysis demonstrated elevated fatty acids and ceramides in db/db at 12 wk, but their levels were decreased at 15 wk, and this was accompanied by persistent mitochondrial ultrastructural abnormalities in concert with evidence of increased fatty acid oxidation and enhanced production of reactive oxygen species. Triacylglyceride and diacylglyceride levels were elevated at both 12 and 15 wk, but their composition changed to consist of more saturated and less unsaturated fatty acyl at 15 wk. An increase in the lipid droplets was apparent at both time points, and this was associated with increases in phosphatidycholine. In conclusion, a distinct pattern of myocardial lipid remodeling, accompanied by oxidative stress, is associated with the onset of diastolic dysfunction in obese, insulin-resistant db/db mice.
Authors:
Vincent G Demarco; David A Ford; Erik J Henriksen; Annayya R Aroor; Megan S Johnson; Javad Habibi; Lixin Ma; Ming Yang; Carolyn J Albert; John W Lally; Caleb A Ford; Mujalin Prasannarong; Melvin R Hayden; Adam T Whaley-Connell; James R Sowers
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-09
Journal Detail:
Title:  Endocrinology     Volume:  154     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-25     Completed Date:  2013-02-22     Revised Date:  2014-07-04    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-71     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / physiology*
Ceramides / metabolism
Fatty Acids / metabolism
Male
Mice
Myocardium / metabolism*
Obesity / metabolism*,  physiopathology*
Oxidative Stress
Phosphatidylcholines / metabolism
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
AG040638/AG/NIA NIH HHS; HL-074214/HL/NHLBI NIH HHS; HL-111906/HL/NHLBI NIH HHS; HL-73101/HL/NHLBI NIH HHS; HL107910/HL/NHLBI NIH HHS; R01 HL073101/HL/NHLBI NIH HHS; R01 HL074214/HL/NHLBI NIH HHS; R01 HL107910/HL/NHLBI NIH HHS; R21 HL111906/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Ceramides; 0/Fatty Acids; 0/Phosphatidylcholines; 0/Reactive Oxygen Species
Comments/Corrections

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


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