TY - JOUR
T1 - Characterisation of the Myocardial Mitochondria Structural and Functional Phenotype in a Murine Model of Diabetic Cardiomyopathy
AU - Parker, Alex M.
AU - Tate, Mitchel
AU - Prakoso, Darnel
AU - Deo, Minh
AU - Willis, Andrew M.
AU - Nash, David M.
AU - Donner, Daniel G.
AU - Crawford, Simon
AU - Kiriazis, Helen
AU - Granata, Cesare
AU - Coughlan, Melinda T.
AU - De Blasio, Miles J.
AU - Ritchie, Rebecca H.
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council (NHMRC) of Australia, including an NHMRC Senior Research Fellowship to RR (ID1059660) and an NHMRC project grant to RR and MJD (ID1158013). This work was also supported in part by the Victorian Government’s Operational Infrastructure Support Programme.
Funding Information:
The authors acknowledge the Monash Histology Platform, the Monash University Monash Micro-Imaging (MMI), and the Ramaciotti Centre for Cryo-Electron Microscopy facility for provision of instrumentation and training. Funding. This work was supported by the National Health and Medical Research Council (NHMRC) of Australia, including an NHMRC Senior Research Fellowship to RR (ID1059660) and an NHMRC project grant to RR and MJD (ID1158013). This work was also supported in part by the Victorian Government?s Operational Infrastructure Support Programme.
Publisher Copyright:
© Copyright © 2021 Parker, Tate, Prakoso, Deo, Willis, Nash, Donner, Crawford, Kiriazis, Granata, Coughlan, De Blasio and Ritchie.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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.
AB - 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.
KW - diabetes
KW - diabetic cardiomyopathy
KW - experimental – animal models
KW - heart
KW - mitochondria
KW - mitochondrial function
UR - http://www.scopus.com/inward/record.url?scp=85115005633&partnerID=8YFLogxK
U2 - 10.3389/fphys.2021.672252
DO - 10.3389/fphys.2021.672252
M3 - Article
AN - SCOPUS:85115005633
SN - 1664-042X
VL - 12
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 672252
ER -