title: Transition from obesity to metabolic syndrome is associated with altered myocardial autophagy and apoptosis.
abstract: 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.
  
  
  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.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Zi-Lun
authors.initials: ZL
authors.lastname: Li
authors.forename: John R
authors.initials: JR
authors.lastname: Woollard
authors.forename: Behzad
authors.initials: B
authors.lastname: Ebrahimi
authors.forename: John A
authors.initials: JA
authors.lastname: Crane
authors.forename: Kyra L
authors.initials: KL
authors.lastname: Jordan
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.forename: Shen-Ming
authors.initials: SM
authors.lastname: Wang
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009765:Obesity / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D013552:Swine