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 less than .01). Increased concentrations of both long-chain acyl-CoA (0.21 +/- 0.03 v 0.06 +/- 0.01 mumol.g dry weight-1 found in STD; P less than .01) and acetyl-CoA (0.17 +/- 0.05 v 0.09 +/- 0.01 found in STD; P less than .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 less than .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.(ABSTRACT TRUNCATED AT 250 WORDS)
Chicco
A
A
Department of Biochemistry, University of Litoral, Santa Fe, Argentina.
Gutman
R
R
Lombardo
Y B
YB
D000105:Acetyl Coenzyme A / Q000032:analysis; D000818:Animals; D002951:Citrates / Q000032:analysis; D019343:Citric Acid; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000032:analysis; D006321:Heart / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D009711:Nucleotides / Q000032:analysis; D010084:Oxidation-Reduction; D010210:Papillary Muscles / Q000737:chemistry / Q000201:enzymology; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D013395:Sucrose / Q000008:administration & dosage
D002951:Citrates; D004040:Dietary Carbohydrates; D004852:Epoxy Compounds; D005227:Fatty Acids; D005958:Glucosephosphates; D007004:Hypoglycemic Agents; D007773:Lactates; D009711:Nucleotides; D011768:Pyruvate Dehydrogenase Complex; D019343:Citric Acid; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D013395:Sucrose; D000105:Acetyl Coenzyme A; C033891:ethyl 2-(5-(4-chlorophenyl)pentyl)oxiran-2-carboxylate