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


CONCLUSIONS
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.
College of Pharmacy, Chungnam National University, 220 Gung-dong, Yuseong-gu, Taejeon, 305-764, Republic of Korea.
Kang Uk
KU
Yun
Chang Seon
CS
Ryu
Jung Min
JM
Oh
Chung Hyun
CH
Kim
Kye Sook
KS
Lee
Chul-Ho
CH
Lee
Hyun-Sun
HS
Lee
Bong-Hee
BH
Kim
Sang Kyum
SK
Kim
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D043383:Adenosylhomocysteinase / Q000235:genetics / Q000378:metabolism; D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D002318:Cardiovascular Diseases / Q000150:complications; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D050558:Cysteine Dioxygenase / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat; D004151:Dipeptides / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D006710:Homocysteine / Q000097:blood*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008716:Methionine Adenosyltransferase / Q000235:genetics / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
D000603:Amino Acids, Sulfur; D004151:Dipeptides; D014280:Triglycerides; D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D050558:Cysteine Dioxygenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D008716:Methionine Adenosyltransferase; D043383:Adenosylhomocysteinase; D003541:Cystathionine beta-Synthase; C017341:gamma-glutamylcysteine