BIOCHEMICAL-ABNORMALITIES IN THE HEART OF RATS FED A SUCROSE-RICH DIET - IS THE LOW ACTIVITY OF THE PYRUVATE-DEHYDROGENASE COMPLEX A RESULT OF INCREASED FATTY-ACID OXIDATION

We have previously shown that normal Wistar rats fed for 3 weeks with an isocaloric sucrose-rich (63%) diet (SRD) develop high levels of plasma free fatty acids and increased triacylglycerol content in the myocardium. We are now reporting that these changes are accompanied by remarkably low levels of the active form of the pyruvate dehydrogenase complex (PDHa; mean ± SEM, 37.2% ± 3.7% of the total activity) when compared with levels found in hearts donated by control rats fed the standard chow diet (STD; 71.0% ± 2.8%; P < .01). Increased concentrations of both long-chain acyl-CoA (0.21 ± 0.03 v 0.06 ± 0.01 μmol · g dry weight-1 found in STD; P < .01) and acetyl-CoA (0.17 ± 0.05 v 0.09 ± 0.01 found in STD; P < .01), as well as a relative decrease in coenzyme A (CoASH) (0.21 ± 0.02 v 0.32 ± 0.05 from STD; P = NS), resulting in an increased acetyl- CoA CoASH ratio (0.80 ± 0.13 v 0.29 ± 0.03 in STD; P < .01) may have stimulated the PDH kinase, leading in turn to an inactivation of the PDH complex. The above enzymatic and metabolic changes in the in situ heart of SRD-fed rats were still present after perfusing them for 35 minutes with a Krebs-Henseleit buffer containing 11 mmol/L glucose as the only exogenous substrate. Since the heart triacylglycerol content at the end of the perfusion was comparable in control and experimental animals, this would indicate that SRD hearts had, in fact, a higher rate of intracellular lipolysis in view that the latter presented a twofold higher triacylglycerol content before starting the perfusion, and that their glycerol output was twofold larger than the one recorded in hearts donated by STD rats. The addition of POCA II (a CPT-I inhibitor) to the perfusate (10 μmol/L) led to a normalization of PDHa levels parallel to a decrease of the acetyl- CoA CoASH ratio and a return of citrate concentrations to normal, strongly suggesting that an increased fatty acid oxidation underlies most if not all of the above metabolic abnormalities found in the heart of SRD-fed rats. The present findings lend further support to our former proposal, that this nutritionally induced syndrome may be an attractive experimental animal model for the study of some pathophysiological mechanisms involved in human non-insulin-dependent diabetes mellitus in general, and to gain insight into the metabolic abnormalities present in the diabetic heart in particular. © 1991.