Brief episode of STZ-induced hyperglycemia produces cardiac abnormalities in rats fed a diet rich in n-6 PUFA

Abstract

Diabetic patients are particularly susceptible to cardiomyopathy independent of vascular disease, and recent evidence implicates cell death as a contributing factor. Given its protective role against apoptosis, we hypothesized that dietary n-6 polyunsaturated fatty acid (PUFA) may well decrease the incidence of this mode of cardiac cell death after diabetes. Male Wistar rats were first fed a diet rich in n-6 PUFA [20% (wt/wt) sunflower oil] for 4 wk followed by streptozotocin (STZ, 55 mg/kg) to induce diabetes. After a brief period of hyperglycemia (4 days), hearts were excised for functional, morphological, and biochemical analysis. In diabetic rats, n-6 PUFA decreased caspase-3 activity, crucial for myocardial apoptosis. However, cardiac necrosis, an alternative mode of cell death, increased. In these hearts, a rise in linoleic acid and depleted cardiac glutathione could explain this "switch" to necrotic cell death. Additionally, mitochondrial abnormalities, impaired substrate utilization, and enhanced triglyceride accumulation could have also contributed to a decline in cardiac function in these animals. Our study provides evidence that, in contrast to other models of diabetic cardiomyopathy that exhibit cardiac dysfunction only after chronic hyperglycemia, n-6 PUFA feeding coupled with only 4 days of diabetes precipitated metabolic and contractile abnormalities in the heart. Thus, although promoted as being beneficial, excess n-6 PUFA, with its predisposition to induce obesity, insulin resistance, and ultimately diabetes, could accelerate myocardial abnormalities in diabetic patients.

Identification of mouse liver mitochondria-associated miRNAs and their potential biological functions

“…Next, we assessed the association of miRNAs with mitochondria and their potential biological relevance through determining the alteration of mitochondriaassociated miRNAs in mouse livers after streptozotocin (STZ) treatment. In agreement with the previous studies showing that STZ induced type 1 diabetes and mitochondria dysfunction [10], we found that STZ treatment led to hyperglycemia (fasting blood glucose ≥12mmol/l). As shown in Figure 1F, the expression pattern of mitochondria-associated miRNAs was significantly altered in STZdiabetic mice.…”

Altered cardiac fatty acid composition and utilization following dexamethasone-induced insulin resistance

“…Rates of glucose oxidation were quantitatively measured by collection of 14 CO2 liberated from [U- 14 C]glucose at the pyruvate dehydrogenase reaction and in the citric acid cycle. To measure cardiac palmitate oxidation, hearts from halothane (2-3%)-anesthetized rats were perfused in the working mode with modified Krebs-Henseleit buffer (including 1.0 mM [9, H]palmitate prebound to 3% BSA, 5.5 mM glucose, 2.0 mM calcium, and 100 U/l insulin) at a preload of 11.5 mmHg, as described previously (11). An afterload of 80 mmHg was maintained, and samples of perfusate and hyamine hydroxide were taken every 10 min for measurement of FA oxidation.…”

Effects of Dietary Polyunsaturated Fatty Acids on Mitochondria

“…A n-3 PUFA rich diet restored the cardiac cardiolipin content in 24 month old rats and prevented the age-specific increase in phosphatidylcholine [26]. On the other hand, n-6 PUFA feeding induced a profound loss of cardiac mitochondrial cardiolipin, abnormal condensed mitochondria and a drop in total ATP [45]. Therefore, any changes in diet composition that alter cardiolipin acyl composition may have a major impact on mitochondrial function and cellular energy metabolism.…”