Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet

Abstract

Purpose: Obesity, a feature of metabolic syndrome, is a risk factor for cardiovascular disease, and elevated plasma homocysteine is associated with increased cardiovascular risk. However, little published information is available concerning the effect of obesity on homocysteine metabolism. Methods: Hepatic homocysteine metabolism was determined in male C57BL/6 mice fed a high-fat diet for 12 weeks. Results: High-fat diet increased plasma homocysteine but decreased hepatic homocysteine levels. Hepatic S-adenosylhomocysteine hydrolase levels were down-regulated in the obese mice, which was in part responsible for the decrease in hepatic S-adenosylmethionine/S- adenosylhomocysteine, which served as an index of transmethylation potential. Despite the decrease in hepatic cysteine, hepatic taurine synthesis was activated via up-regulation of cysteine dioxygenase. Hepatic levels of methionine adenosyltransferase I/III, methionine synthase, methylene tetrahydrofolate reductase, and gamma-glutamylcysteine ligase catalytic subunit were unchanged. Obese mice showed elevated betaine-homocysteine methyltransferase and decreased cystathionine beta-synthase activities, although the quantities of these enzymes were unchanged. Conclusion: This study suggests that plasma homocysteine level is increased in obesity-associated hepatic steatosis, possibly as a result of increased hepatic homocysteine efflux along with an altered sulfur amino acid metabolism.