Dependence of Cardiac Systolic Function on Elevated Fatty Acid Availability in Obese, Insulin-Resistant Rats.
BACKGROUND
Clinical data advocating an adverse effect of obesity on left ventricular (LV) systolic function independent of comorbidities is controversial. We hypothesized that in obesity with prediabetic insulin resistance, circulating fatty acids (FAs) become a valuable fuel source in the maintenance of normal systolic function.


METHODS
Male Wistar rats were fed a high caloric diet for 32 weeks to induce obesity. Myocardial LV systolic function was assessed using echocardiography and isolated heart preparations.


RESULTS
Aortic output was reduced in obese rat hearts over a range of filling pressures (for example: 15 cmH2O, obese: 32.6 ± 1.2 ml/min vs control: 46.2 ± 0.9 ml/min, P < .05) when perfused with glucose alone. Similarly, the slope of the LV end-systolic pressure-volume relationship decreased, and there was a right shift in the LV end-systolic stress-strain relationship as determined in Langendorff perfused, isovolumic rat heart preparations in the presence of isoproterenol (10(-8)M) (LV systolic stress-strain relationship and a reduced load-independent intrinsic systolic myocardial function, obese: 791 ± 62 g/cm(2) vs control: 1186 ± 74 g/cm(2), P < .01). The addition of insulin to the perfusion buffer improved aortic output, whereas the addition of FAs completely normalized aortic output. LV function was maintained in obese animals in vivo during an inotropic challenge.


CONCLUSIONS
Elevated circulating FA levels may be important to maintain myocardial systolic function in the initial stages of obesity and insulin resistance.
Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, PO BOX 19063, Tygerberg 7505, South Africa; Hypertension in Africa Research Team (HART), North West University, Private Bag X6001, Potchefstroom 2520, South Africa.
Wayne
W
Smith
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
Gavin R
GR
Norton
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, Johannesburg, South Africa.
Angela J
AJ
Woodiwiss
Department of Biomedical Sciences, Faculty of Health Sciences, University of Stellenbosch, PO BOX 19063, Tygerberg 7505, South Africa.
Amanda
A
Lochner
The School of Medical Science, Griffith University, Gold Coast Campus, Southport, QLD 4217, Australia. Electronic address: j.dutoit@griffith.edu.au.
Eugene F
EF
du Toit
D000818:Animals; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology*; D000067268:Isolated Heart Preparation; D008297:Male; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D005227:Fatty Acids; D007328:Insulin; D005947:Glucose
Obesity; cardiac systolic function; fatty acids