Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy

Alex M. Parker, Mitchel Tate, Darnel Prakoso, Minh Deo, Andrew M. Willis, David M. Nash, Daniel G. Donner, Simon Crawford, Helen Kiriazis, Cesare Granata, Melinda T. Coughlan, Miles J. De Blasio, Rebecca H. Ritchie

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6 Citations (Scopus)

Abstract

People affected by diabetes are at an increased risk of developing heart failure than their non-diabetic counterparts, attributed in part to a distinct cardiac pathology termed diabetic cardiomyopathy. Mitochondrial dysfunction and excess reactive oxygen species (ROS) have been implicated in a range of diabetic complications and are a common feature of the diabetic heart. In this study, we sought to characterise impairments in mitochondrial structure and function in a recently described experimental mouse model of diabetic cardiomyopathy. Diabetes was induced in 6-week-old male FVB/N mice by the combination of three consecutive-daily injections of low-dose streptozotocin (STZ, each 55 mg/kg i.p.) and high-fat diet (42% fat from lipids) for 26 weeks. At study end, diabetic mice exhibited elevated blood glucose levels and impaired glucose tolerance, together with increases in both body weight gain and fat mass, replicating several aspects of human type 2 diabetes. The myocardial phenotype of diabetic mice included increased myocardial fibrosis and left ventricular (LV) diastolic dysfunction. Elevated LV superoxide levels were also evident. Diabetic mice exhibited a spectrum of LV mitochondrial changes, including decreased mitochondria area, increased levels of mitochondrial complex-III and complex-V protein abundance, and reduced complex-II oxygen consumption. In conclusion, these data suggest that the low-dose STZ-high fat experimental model replicates some of the mitochondrial changes seen in diabetes, and as such, this model may be useful to study treatments that target the mitochondria in diabetes.

Original languageEnglish
Article number672252
Number of pages14
JournalFrontiers in Physiology
Volume12
DOIs
Publication statusPublished - 1 Sept 2021

Keywords

  • diabetes
  • diabetic cardiomyopathy
  • experimental – animal models
  • heart
  • mitochondria
  • mitochondrial function

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