Hyperhomocysteinemia as a component of syndrome X
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.
References (47)
- et al.
Coronary artery disease risk predicted by insulin resistance, plasma lipids, and hypertension in people without diabetes
Am J Med Sci
(2000) - et al.
Homocysteine and myocardial infarction
Atherosclerosis
(1988) - et al.
Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men
Lancet
(1995) - et al.
Regulation of homocysteine metabolism
Adv Enzyme Regul
(1999) - et al.
Plasma homocysteine concentrations are regulated by acute hyperinsuliemia in nondiabetic but not type 2 diabetic subjects
Metabolism
(1998) - et al.
Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal
Atherosclerosis
(1999) - et al.
Elevated plasma total homocysteine levels in hyperinsulinemic obese subjects
J Nutr Biochem
(2002) - et al.
Plasma homocysteine concentrations and insulin sensitivity in hypertensive subjects
Am J Heart
(2000) - et al.
The effect of glucose and insulin on the activity of methylene tetrahydrofolate reductase and cystathionine-β-synthaseStudies in hepatocytes
Atherosclerosis
(2001) - et al.
Effects of a high-fat-sucrose diet on enzymes in homocysteine metabolism in the rat
Metabolism
(2000)
The cardiovascular risk factor plasminogen activator inhibitor type I is related to insulin resistance
Metabolism
Insulin resistanceA multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia and atherosclerotic cardiovascular disease
Diabetes Care
Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population
Diabetologia
Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged menThe 22-year follow-up results of the Helsinki Policemen Study
Circulation
Insulin resistance, high prevalence of diabetes, and cardiovascular risk in immigrant AsiansGenetic or environmental effect?
Br Heart J
Hyperinsulinemia as an independent risk factor for ischemic heart disease
N Engl J Med
Role of insulin resistance in human disease
Diabetes
Triglycerides as a risk factor for coronary artery disease
Am J Cardiol
High blood pressure role in coronary heart disease and implication for prevention and control
Executive Summary of The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII)
JAMA
Plasma total homocysteine, B vitamins and risk of coronary atherosclerosis
Arterioscler Thromb Vasc Biol
HyperhomocysteinemiaAn independent risk factor for vascular disease
N Engl J Med
Plasma homocysteine as a risk factor for vascular disease. European Concerted Action Project
JAMA
Cited by (61)
Homocysteine promotes hepatic steatosis by activating the adipocyte lipolysis in a HIF1α-ERO1α-dependent oxidative stress manner
2020, Redox BiologyCitation Excerpt :HHcy has been established as an independent risk factor for cardiovascular disease in humans [5]. The epidemiological literature also indicates that HHcy is associated with insulin resistance and which is considered a chronic inflammatory status [6,7]. Previously, we have showed that Hcy induces insulin resistance in mice by regulating the expression and secretion of resistin from adipose tissue [8].
Time-response studies on development of cognitive deficits in an experimental model of insulin resistance
2019, Clinical NutritionCitation Excerpt :Elevated Hcy levels in the blood can stimulate hyperphosphorylation of tau, intensification of Aβ level in the brain, interrupt DNA repair in the neurons hippocampus and make the neurons even more susceptible to the amyloid toxicity [46]. Fructose enrich diet fed rats have shown 72 percent higher homocysteine levels after 5 weeks compared to normal chow-fed controls [47]. In our experiment, we have observed a 4.83 fold increased serum homocysteine level as compared to normal pellet chow group at 24th week.
Pharmacophore modeling, virtual screening, molecular docking studies and density functional theory approaches to identify novel ketohexokinase (KHK) inhibitors
2015, BioSystemsCitation Excerpt :The chronic high-fructose diets elevate free fatty acids and triglycerides, which impair glucose usage in muscle tissue and increase the rate of lipolysis in adipose tissue (Mayes, 1993). The elevated triglycerides could impede insulin-signaling pathways (Dresner et al., 1999; Koteish and Diehl, 2001; Ueno et al., 2000), support chronic inflammation (Holven et al., 2006; Oron-Herman et al., 2003; Wu et al., 2004), and lead to glyco lipid toxicity (Swanson et al., 1992) with the possible failure of pancreatic β-cells (Lewis et al., 2002). The hepatic fructokinase deficiency is caused by recessive mutations in KHK gene.
B-vitamins and metabolic syndrome in Mesoamerican children and their adult parents
2021, Public Health NutritionHigh-fructose intake-induced dyslipidemia and oxidative stress accompanied by hippocampal dysfunctions in hypertensive but not hypertriacylglycerolemic rats
2023, General Physiology and BiophysicsThe causative mechanisms of hyperhomocysteinemia and obesity
2021, Nutritional Management and Metabolic Aspects of Hyperhomocysteinemia