Elsevier

Metabolism

Volume 52, Issue 11, November 2003, Pages 1491-1495
Metabolism

Hyperhomocysteinemia as a component of syndrome X

https://doi.org/10.1016/S0026-0495(03)00262-2Get rights and content

Abstract

Syndrome X, a cluster of several metabolic disorders that includes hyperinsulinemia, hypertriglyceridemia, and hypertension, is associated with severe vascular morbidity. Hyperhomocysteinemia is another risk factor for cardiovascular and cerebrovascular diseases, often exhibited by insulin-resistant patients. In the current study, we investigated the relationship between syndrome X and hyperhomocysteinemia in a rat model. Two groups of rats were fed either fructose-enriched diet or standard rat chow for 5 weeks. Systolic blood pressure (SBP), as well as fasting plasma insulin, triglycerides, total cholesterol, and total homocysteine levels, were determined at the beginning and at the end of the study. A complete metabolic syndrome was induced by the fructose-enriched diet, including hyperinsulinemia, hypertriglyceridemia, and hypertension. Homocysteine concentration was 72% higher after 5 weeks on the fructose diet (8.49 ± 1.6 v 4.92 ± 0.9 μmol/l, P < .01). Insulin, triglycerides, SBP, and homocysteine levels were insignificantly changed during 5 weeks on standard rat chow. Homocysteine was positively and significantly correlated with any original component of syndrome X (r = 0.565, P = .014 with insulin, r = 0.662, P = .001 with triglycerides, and r = 0.774, P < .001 with SBP). The results of the present study indicate that hyperhomocysteinemia is an integral component of this rat model of syndrome X. It is thus highly likely that hyperhomocysteinemia is an integral component of the human syndrome X as well, and thereby contributes to the overall high vascular risk associated with this condition.

Section snippets

Animals, diets, and study design

Twenty male Sprague-Dawley rats weighing 200 ± 20 g were purchased from Harlan, Israel. The animals were kept on a 14 hour/10 hour light/dark cycle and at a constant temperature (22°C). Food and water were supplied ad libitum. All rats were fed a standard rat chow prior to beginning the study, and then divided randomly into 2 equal groups. For 5 weeks the control group continued to consume standard rat chow (Koffolk, Israel) composed of 21% protein, 4% fat, 50% carbohydrate (vegetable starch),

Results

The effect of fructose feeding on SBP is illustrated in Fig 1. SBP rose significantly from 125.6 ± 9.5 to 146.3 ± 5.0 mm Hg (P < .001) during the fructose feeding period, while there was no significant elevation in the control group (121.9 ± 3.7 v 123.9 ± 4.7 mm Hg, P > .05).

Fig 2 summarizes the metabolic effects of 5 weeks of fructose feeding. Plasma insulin level doubled from 22.4 ± 6 to 43.2 ± 15.8 μU/mL (P < .001); triglycerides increased 3.5-fold from 91.8 ± 23.4 to 322.3 ± 93.5 mg/dL (P

Discussion

The results of the present study lend further support to a possible regulatory role of insulin in the metabolism of homocysteine. They also indicate that hyperhomocysteinemia is an integral component of syndrome X. The metabolic syndrome obtained using fructose-fed rats included an impressive rise of insulin, SBP, and triglycerides, as was expected. In addition, a significant elevation of plasma homocysteine level was inducd. Correlation coefficients between homocysteine and other components of

Acknowledgements

This work was performed in partial fulfillment of the requirements for a PhD degree of Mor Oron-Herman, Sackler Faculty of Medicine, Tel Aviv University, Israel.

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