Impaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre-diabetes.
OBJECTIVE
Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre-diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion.


METHODS
Eight-week-old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age-matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation.


RESULTS
Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high-density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia-reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress-induced damage.


CONCLUSIONS
These data show that decreased mitochondrial bioenergetic capacity in pre-diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation.
Essop
M F
MF
Department of Physiological Sciences, Stellenbosch University, South Africa. mfessop@sun.ac.za
Anna Chan
W Y
WY
Valle
A
A
García-Palmer
F J
FJ
Du Toit
E F
EF
D000818:Animals; D001835:Body Weight; D019069:Cell Respiration / Q000502:physiology*; D004032:Diet; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D010101:Oxygen Consumption / Q000502:physiology; D011236:Prediabetic State / Q000209:etiology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar