Experimental hyperhomocysteinaemia: differences in tissue metabolites between homocystine and methionine feeding in a rat model

Aim:  Hyperhomocysteinaemia, diagnosed by serum levels, is regarded as an independent risk indicator for cardiovascular events and is associated with various diseases. The pathomechanisms seem to be partly due to concentrations of homocysteine metabolites and their effect on the cellular transmethylation processes. Methods:  We compared two common models for experimental hyperhomocysteinaemia – high methionine diet and homocystine-enriched diet – regarding their effects on tissue concentrations of homocysteine metabolites. Results:  Both diets induced hyperhomocysteinaemia without affecting renal function or vitamine status. However, the tissue contents of homocysteine and its precursors S-adenosyl-homocysteine (SAH) and S-adenosyl-methionine exhibited major differences between both models. Transmethylation potential was elevated 1.7-fold in liver of rats fed the methionine diet, whereas it was unaltered after homocystine-enriched diet. Kidneys of rats fed the methionine diet did not show any alterations in tissue content of homocysteine and its precursors, whereas in the homocystine group homocysteine and the transmethylation inhibitor SAH were elevated from 23.1 ± 10.4 to 78.0 ± 26.0 nmol g−1 and from 106 ± 4 to 170 ± 22 nmol g−1 respectively. Homocysteine tissue content was elevated in the homocystine, but not in the methionine group. Conclusions:  Alterations to homocysteine metabolism are distinct in both models. These findings may explain divergent results, which have been published for these models of hyperhomocysteinaemia and which have resulted in controversial discussions in the past.