title: Moderate ethanol administration accentuates cardiomyocyte contractile dysfunction and mitochondrial injury in high fat diet-induced obesity.
abstract: Light to moderate drinking confers cardioprotection although it remains unclear with regards to the role of moderate drinking on cardiac function in obesity. This study was designed to examine the impact of moderate ethanol intake on myocardial function in high fat diet intake-induced obesity and the mechanism(s) involved with a focus on mitochondrial integrity. C57BL/6 mice were fed low or high fat diet for 16 weeks prior to ethanol challenge (1g/kg/d for 3 days). Cardiac contractile function, intracellular Ca(2+) homeostasis, myocardial histology, and mitochondrial integrity [aconitase activity and the mitochondrial proteins SOD1, UCP-2 and PPARγ coactivator 1α (PGC-1α)] were assessed 24h after the final ethanol challenge. Fat diet intake compromised cardiomyocyte contractile and intracellular Ca(2+) properties (depressed peak shortening and maximal velocities of shortening/relengthening, prolonged duration of relengthening, dampened intracellular Ca(2+) rise and clearance without affecting duration of shortening). Although moderate ethanol challenge failed to alter cardiomyocyte mechanical property under low fat diet intake, it accentuated high fat diet intake-induced changes in cardiomyocyte contractile function and intracellular Ca(2+) handling. Moderate ethanol challenge failed to affect fat diet intake-induced cardiac hypertrophy as evidenced by H&E staining. High fat diet intake reduced myocardial aconitase activity, downregulated levels of mitochondrial protein UCP-2, PGC-1α, SOD1 and interrupted intracellular Ca(2+) regulatory proteins, the effect of which was augmented by moderate ethanol challenge. Neither high fat diet intake nor moderate ethanol challenge affected protein or mRNA levels as well as phosphorylation of Akt and GSK3β in mouse hearts. Taken together, our data revealed that moderate ethanol challenge accentuated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies as well as mitochondrial injury.
authors.affiliation: Department of Orthopedics, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
authors.affiliation: Wound Healing and Cell Biology Laboratory, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100853, PR China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Lei
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Qiurong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.
authors.forename: Lucy B
authors.initials: LB
authors.lastname: Esberg
authors.affiliation: Department of Civil and Architectural Engineering, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Zaixing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: University of North Dakota School of Medicine, Grand Forks, ND 58201, USA.
authors.forename: Glenda I
authors.initials: GI
authors.lastname: Scott
authors.affiliation: Cardiology Department, Tang Du Hospital, Xi'an, Shaanxi 710038, PR China. Electronic address: lxhlyh@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, University of Wyoming, Laramie, WY 82071, USA. Electronic address: jren@uwyo.edu.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000079:Acetaldehyde / Q000097:blood; D000818:Animals; D002118:Calcium / Q000378:metabolism; D059305:Diet, High-Fat; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000032:analysis; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology
chemical_list: D024101:Mitochondrial Proteins; D000431:Ethanol; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000079:Acetaldehyde; D002118:Calcium
keywords: Cardiomyocyte shortening; Ethanol; Intracellular Ca(2+) transient; Mitochondria; Obesity