Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

Abstract

BackgroundSaturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve.Materials and methodsRats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated.ResultsAlthough all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway.ConclusionsNascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals.

Long-term abdominal adiposity activates several parameters of cardiac energy function

“…The WD utilized in this study for 8 months increased noticeably abdominal adiposity without changing animal weight. Although we recently published [20] that such a diet can trigger systemic glucose intolerance after a 3-month administration, we were unable to observe the same effect after the 8-month distribution, suggesting that an adaptation occurred. The ex vivo cardiac mechanical function as measured by the rate pressure product was not significantly altered, although the left ventricle-developed pressure was greatly reduced.…”

“…It was then rapidly (less than 1 min from the chest opening to avoid problem of cellular damages and preconditioning) perfused at constant pressure according to a modified Langendorff method [19,20] with a Krebs-Henseleit buffer containing (in mM) NaCl 119, MgSO 4 1.2, KCl 4.8, NaHCO 3 25, KH 2 PO 4 1.2, CaCl 2 1.2, and glucose 11 mM as sole energy substrate. The buffer was maintained at 37°C and continuously oxygenated with carbogen (95 % O 2 / 5 % CO 2 ).…”

“…Oral glucose tolerance test (OGTT) was performed 2 weeks before the sacrifice as previously described [20]. On the day of the experiment, the rats were weighed, anesthetized with intraperitoneal injection of sodium pentobarbital (60 mg/kg), and heparinized (1000 IU/kg) via the saphenous vein before their sacrifice.…”

“…Thus, obesity-related activation of renine-angiotensin-aldosterone system can stretch cardiomyocytes and increase contractility according to the Starling's law, and/or activation of the β-adrenergic system observed in obesity can stimulate the heart. This augmented in vivo contractility was sustained by an increased coronary reactivity to acetylcholine [20], can lead to a long-term mechanical stimulation of the heart, and can stimulate the energy metabolism. This can increase cardiac fitness and survival rate during/after cardiovascular events.…”

“…However, we and other searchers have observed that abdominal obesity induced by a Western diet [20] and perinatal overfeeding [8] can augment in vivo cardiac function. In contrast, mechanical function measured ex vivo in perfectly standardized conditions is not modified.…”