Effects of a high-fat-sucrose diet on enzymes in homocysteine metabolism in the rat

Vivian Fonseca, Aliza Dicker-Brown, Subramanian Ranganathan, Wei Song, R. James Barnard, Louis Fink, Philip A. Kern

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Hyperhomocysteinemia (HH) and hyperinsulinemia are both risk factors for cardiovascular disease. To examine the effects of hyperinsulinemia on homocysteine metabolism, we fed rats a high-fat-sucrose (HFS) diet and then measured the hepatic mRNA and activity of 2 key enzymes involved in this metabolic pathway: 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine-β-synthase (CβS). Fischer rats made insulin-resistant by a HFS diet were examined at 6 months and 2 years of age and compared with control rats fed a low-fat, complex-carbohydrate (LFCC) diet. At the end of 6 months, the HFS rats were heavier than the LFCC rats (214 ± 3.4 v 188 ± 1.4 g, P < .01). There were no differences in blood glucose between HFS and LFCC rats; however, plasma insulin and homocysteine concentrations were elevated in HFS rats (insulin, 56 ± 12 v 14.5 ± 2.9 μU/mL; homocysteine, 10.77 ± 0.9 v 6.89 ± 0.34 μmol/L, P < .01). Hepatic CβS enzyme activity was significantly lower in HFS compared with LFCC rats (0.45 v 0.64 U/mg, P = .0001), and this decrease was reflected in a decrease of the CβS mRNA concentration. In contrast, hepatic MTHFR enzyme activity and mRNA concentration were significantly elevated in the HFS group compared with controls (HFS and LFCC, 8.62 and 4.8 nmol/h/mg protein, respectively, P = .0001). These changes in plasma homocysteine, CβS, and MTHFR were significantly correlated with the degree of obesity and hyperinsulinemia. Fasting plasma insulin correlated significantly and positively with plasma homocysteine (r = .51, P < .01) and MTHFR activity (r = .48, P < .01) and negatively with CβS activity (r = -.54, P < .001). CβS and MTHFR activities were inversely correlated with each other (r = -.58, P < .001). In conclusion, rats fed a HFS diet are hyperinsulinemic, and the hyperinsulinemia is associated with an elevated homocysteine concentration and changes in 2 key enzymes in homocysteine metabolism. Copyright (C) 2000 by W.B. Saunders Company.

Original languageEnglish (US)
Pages (from-to)736-741
Number of pages6
JournalMetabolism: clinical and experimental
Issue number6
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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