Document Detail


Transition from obesity to metabolic syndrome is associated with altered myocardial autophagy and apoptosis.
MedLine Citation:
PMID:  22383702     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Transition from obesity to metabolic-syndrome (MetS) promotes cardiovascular diseases, but the underlying cardiac pathophysiological mechanisms are incompletely understood. We tested the hypothesis that development of insulin resistance and MetS is associated with impaired myocardial cellular turnover.
METHODS AND RESULTS: MetS-prone Ossabaw pigs were randomized to 10 weeks of standard chow (lean) or to 10 (obese) or 14 (MetS) weeks of atherogenic diet (n=6 each). Cardiac structure, function, and myocardial oxygenation were assessed by multidetector computed-tomography and Blood Oxygen Level-Dependent-MRI, the microcirculation with microcomputed-tomography, and injury mechanisms by immunoblotting and histology. Both obese and MetS showed obesity and dyslipidemia, whereas only MetS showed insulin resistance. Cardiac output and myocardial perfusion increased only in MetS, yet Blood Oxygen Level-Dependent-MRI showed hypoxia. Inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis also increased in both obese and MetS, but more pronouncedly in MetS. Furthermore, autophagy in MetS was decreased and accompanied by marked apoptosis.
CONCLUSIONS: Development of insulin resistance characterizing a transition from obesity to MetS is associated with progressive changes of myocardial autophagy, apoptosis, inflammation, mitochondrial dysfunction, and fibrosis. Restoring myocardial cellular turnover may represent a novel therapeutic target for preserving myocardial structure and function in obesity and MetS.
Authors:
Zi-Lun Li; John R Woollard; Behzad Ebrahimi; John A Crane; Kyra L Jordan; Amir Lerman; Shen-Ming Wang; Lilach O Lerman
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-01
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-20     Completed Date:  2012-07-10     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1132-41     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Autophagy*
Diet, Atherogenic / adverse effects
Disease Models, Animal
Disease Progression
Insulin Resistance*
Metabolic Syndrome X / etiology*,  metabolism,  pathology
Myocardium / metabolism,  pathology*
Obesity / complications*,  metabolism,  pathology
Oxidative Stress
Swine
Grant Support
ID/Acronym/Agency:
C06 RR018898/RR/NCRR NIH HHS; C06 RR018898-01/RR/NCRR NIH HHS; C06-RR018898/RR/NCRR NIH HHS; DK73608/DK/NIDDK NIH HHS; HL085307/HL/NHLBI NIH HHS; HL77131/HL/NHLBI NIH HHS; P01 HL085307/HL/NHLBI NIH HHS; P01 HL085307-05/HL/NHLBI NIH HHS; R01 DK073608/DK/NIDDK NIH HHS; R01 DK073608-06/DK/NIDDK NIH HHS; R01 HL077131/HL/NHLBI NIH HHS; R01 HL077131-08/HL/NHLBI NIH HHS
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