Plasma homocysteine level and hepatic sulfur amino acid metabolism in mice fed a high-fat diet |
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Authors: | Kang Uk Yun Chang Seon Ryu Jung Min Oh Chung Hyun Kim Kye Sook Lee Chul-Ho Lee Hyun-Sun Lee Bong-Hee Kim Sang Kyum Kim |
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Institution: | 1. College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Taejeon, 305-764, Republic of Korea 2. Laboratory of Experimental Animals, KRIBB, Yuseong-gu, Taejeon, Republic of Korea 3. Molecular Cancer Research Center, KRIBB, Ochang, Cheongwon, Chungbuk, Republic of Korea
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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. |
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