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Circulation. 2014 Aug 12;130(7):554-64. doi: 10.1161/CIRCULATIONAHA.113.008476. Epub 2014 Jun 13.

Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients.

Author information

1
From the Department of Physiology, Faculty of Medicine Lille, Lille, France (D.M., X.M., A.C., N.D., C.P., S.M., S.P., R.N.); Service d'Explorations Fonctionnelles CardioVasculaires (D.M., A.C., S.M.), Department of Cardiovascular Surgery (T.M., G.F., J.-M.E.A., M.K.), and Biochemistry Division, Pathology and Biology Center (F.Z.), University Hospital of Lille, Lille, France; Université Lille 2, Inserm, U1011, and Institut Pasteur de Lille, Lille, France (D.M., X.M., Y.S., H.D., P.L., B.S.); University Hospital of Lille, Lille, France; INSERM U1096, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France (I.R.-J., V.R.); and EA4483-Département de Médecine du Travail, Faculty of Medicine; University Lille 2, Lille, France (J.-L.E.). davidmontaigne@hotmail.com bart.staels@pasteur-lille.fr.
2
From the Department of Physiology, Faculty of Medicine Lille, Lille, France (D.M., X.M., A.C., N.D., C.P., S.M., S.P., R.N.); Service d'Explorations Fonctionnelles CardioVasculaires (D.M., A.C., S.M.), Department of Cardiovascular Surgery (T.M., G.F., J.-M.E.A., M.K.), and Biochemistry Division, Pathology and Biology Center (F.Z.), University Hospital of Lille, Lille, France; Université Lille 2, Inserm, U1011, and Institut Pasteur de Lille, Lille, France (D.M., X.M., Y.S., H.D., P.L., B.S.); University Hospital of Lille, Lille, France; INSERM U1096, University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France (I.R.-J., V.R.); and EA4483-Département de Médecine du Travail, Faculty of Medicine; University Lille 2, Lille, France (J.-L.E.).

Abstract

BACKGROUND:

Obesity and diabetes mellitus are independently associated with the development of heart failure. In this study, we determined the respective effects of obesity, insulin resistance, and diabetes mellitus on the intrinsic contraction and mitochondrial function of the human myocardium before the onset of cardiomyopathy.

METHODS AND RESULTS:

Right atrial myocardium was obtained from 141 consecutive patients presenting no sign of cardiomyopathy. We investigated ex vivo isometric contraction, mitochondrial respiration and calcium retention capacity, and respiratory chain complex activities and oxidative stress status. Diabetes mellitus was associated with a pronounced impairment of intrinsic contraction, mitochondrial dysfunction, and increased myocardial oxidative stress, regardless of weight status. In contrast, obesity was associated with less pronounced contractile dysfunction without any significant perturbation of mitochondrial function or oxidative stress status. Tested as continuous variables, glycated hemoglobin A1C, but neither body mass index nor the insulin resistance index (homeostasis model assessment-insulin resistance), was independently associated with cardiac mitochondrial function. Furthermore, diabetes mellitus was associated with cardiac mitochondrial network fragmentation and significantly decreased expression of the mitochondrial fusion related protein MFN1. Myocardial MFN1 content was inversely proportional to hemoglobin A1C.

CONCLUSION:

Worsening of intrinsic myocardial contraction in the transition from obesity to diabetes mellitus is likely related to worsening of cardiac mitochondrial function because impaired mitochondrial function and dynamics and contractile dysfunction are observed in diabetic patients but not in "metabolically healthy" obese patients at early stage in insulin resistance.

KEYWORDS:

autophagy; diabetes mellitus, type 2; mitochondria; mitochondrial dynamics; obesity

[Indexed for MEDLINE]

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