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Open Access Original investigation

Cardiac contractile function and mitochondrial respiration in diabetes-related mouse models

Camille Marciniak, Xavier Marechal, David Montaigne, Remi Neviere and Steve Lancel*

Author Affiliations

EA 4484 – Physiology Department, Faculty of Medicine, Lille 2 University, 1, place de Verdun, Lille 59045, France

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Cardiovascular Diabetology 2014, 13:118  doi:10.1186/s12933-014-0118-7

Published: 21 August 2014

Abstract

Background

Pathophysiological processes underlying diabetic-related cardiomyopathies are complex. Mitochondria dysfunction is often described as a cause of cardiac impairment but its extent may depend on the type of experimental diabetes. Here we proposed to compare drug- or diet-induced models of diabetes in terms of metabolic features, cardiac and mitochondrial functions.

Methods

Mice were fed with regular chow or fat-enriched diet. After three weeks, they received either citrate or streptozotocin injections for five consecutive days. Metabolic parameters, myocardial contractile function and mitochondrial respiration were measured after three more weeks. Fat mass volumes were assessed by magnetic resonance imaging. Oral glucose tolerance test, insulin tolerance test, triglyceride and adipocytokine quantification were evaluated to establish metabolic profiles. Cardiac function was assessed ex vivo onto a Langendorff column. Isolated cardiac mitochondria respiration was obtained using high-resolution oxygraphy.

Results

Mice fed with the fat-enriched regimen presented abdominal obesity, increased blood glucose, elevated leptin level, glucose intolerance, and insulin resistance. Mice treated with streptozotocin, independently of the regimen, lost their capacity to release insulin in response to glucose ingestion. Mice fed with regular chow diet and injected with streptozotocin developed cardiac dysfunction without mitochondrial respiration defect. However, both groups of high-fat diet fed mice developed cardiac alterations associated with reduction in mitochondrial oxygen consumption, despite an increase in mitochondrial biogenesis signalling.

Conclusions

We explored three animal models mimicking type 1 and 2 diabetes. While cardiac dysfunction was present in the three groups of mice, mitochondrial respiration impairment was only obvious in models reproducing features of type 2 diabetes.

Keywords:
Metabolic syndrome; Diabetes; Heart; Mitochondria; Respiration; Streptozotocin; High-fat diet