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

doi:10.1053/meta.2000.6256

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 journal › Article › peer-review

84 Scopus citations

Abstract

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 language	English
Pages (from-to)	736-741
Number of pages	6
Journal	Metabolism: Clinical and Experimental
Volume	49
Issue number	6
DOIs	https://doi.org/10.1053/meta.2000.6256
State	Published - 2000

Bibliographical note

Funding Information:
From the Department of Medicine, Division of Endocrinology, and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock Central Arkansas Veterans Healthcare System, Little Rock, AR; and Department of Physiological Science, University of California at Los Angeles, Los Angeles, CA. Submitted May 14, 1999; accepted December 2, 1999. Supported in part by a grant from the American Heart Association Arkansas Affiliate, a Medical Research Endowment Grant from the University of Arkansas for Medical Sciences, a Veterans Administration Merit Grant (P.A.K.), N1H Grant No. DK39176 (P.A.K.), NIH grant No. AG09592 (R.J.B.), and the Jon Holden DeHaan Foundation (R.J.B.). Address reprint requests to Vivian Fonseea, MD, Department of Medicine, Section of Endocrinology SL53, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. Copyright © 2000 by W.B. Saunders Company 0026-0495/00/4906-001651 O.0 0/0 doi: l O.l O53/meta.2000.6256

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Endocrinology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1053/meta.2000.6256

Cite this

@article{10946c3ff1f54bfb9312986bc708ea01,

title = "Effects of a high-fat-sucrose diet on enzymes in homocysteine metabolism in the rat",

abstract = "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.",

author = "Vivian Fonseca and Aliza Dicker-Brown and Subramanian Ranganathan and Wei Song and Barnard, {R. James} and Louis Fink and Kern, {Philip A.}",

note = "Funding Information: From the Department of Medicine, Division of Endocrinology, and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock Central Arkansas Veterans Healthcare System, Little Rock, AR; and Department of Physiological Science, University of California at Los Angeles, Los Angeles, CA. Submitted May 14, 1999; accepted December 2, 1999. Supported in part by a grant from the American Heart Association Arkansas Affiliate, a Medical Research Endowment Grant from the University of Arkansas for Medical Sciences, a Veterans Administration Merit Grant (P.A.K.), N1H Grant No. DK39176 (P.A.K.), NIH grant No. AG09592 (R.J.B.), and the Jon Holden DeHaan Foundation (R.J.B.). Address reprint requests to Vivian Fonseea, MD, Department of Medicine, Section of Endocrinology SL53, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. Copyright {\textcopyright} 2000 by W.B. Saunders Company 0026-0495/00/4906-001651 O.0 0/0 doi: l O.l O53/meta.2000.6256",

year = "2000",

doi = "10.1053/meta.2000.6256",

language = "English",

volume = "49",

pages = "736--741",

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T1 - Effects of a high-fat-sucrose diet on enzymes in homocysteine metabolism in the rat

AU - Fonseca, Vivian

AU - Dicker-Brown, Aliza

AU - Ranganathan, Subramanian

AU - Song, Wei

AU - Barnard, R. James

AU - Fink, Louis

AU - Kern, Philip A.

N1 - Funding Information: From the Department of Medicine, Division of Endocrinology, and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock Central Arkansas Veterans Healthcare System, Little Rock, AR; and Department of Physiological Science, University of California at Los Angeles, Los Angeles, CA. Submitted May 14, 1999; accepted December 2, 1999. Supported in part by a grant from the American Heart Association Arkansas Affiliate, a Medical Research Endowment Grant from the University of Arkansas for Medical Sciences, a Veterans Administration Merit Grant (P.A.K.), N1H Grant No. DK39176 (P.A.K.), NIH grant No. AG09592 (R.J.B.), and the Jon Holden DeHaan Foundation (R.J.B.). Address reprint requests to Vivian Fonseea, MD, Department of Medicine, Section of Endocrinology SL53, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112. Copyright © 2000 by W.B. Saunders Company 0026-0495/00/4906-001651 O.0 0/0 doi: l O.l O53/meta.2000.6256

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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