Site of Vanadium Inhibition of Cholesterol Biosynthesis

Azarnoff, Daniel L.; Curran, George L.

doi:10.1021/ja01568a074

Cited by 42 publications

(7 citation statements)

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“…Furthermore, NaMV and VS decreased plasma cholesterol levels in humans [86,90,100], without alteration of either plasma free fatty acid or triglyceride fractions [86,89]. Vanadate has also been shown to reduce total and free cholesterol levels in normal subjects [101], which may be due to inhibition of the steps involved in cholesterol biosynthesis [102,103]. In isolated hepatocytes [104] and adipocytes [24], NaOV modulated lipid metabolism by stimulating lipogenesis and suppressing lipolytic activity.…”

Section: Effect On Lipogenesis and Lipolysismentioning

confidence: 99%

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

2004

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Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.

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Section: Effect On Lipogenesis and Lipolysismentioning

confidence: 99%

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

2004

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“…One such specific inhibitor is the metal vanadium. Salts of vanadium have been shown to inhibit the utilization of mevalonic acid for cholesterol biosynthesis (2), to inhibit cholesterol biosynthesis in vitro and in vivo (3), to induce mobilization of predeposited aortic cholesterol in rabbits (4) and to lessen the deposition of cholesterol in rabbits (5) and in birds (6) fed high cholesterol diets.…”

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confidence: 99%

Effect of Cholesterol Synthesis Inhibition in Normocholesteremic Young Men*

Curran¹,

Azarnoff²,

Bolinger³

1959

J. Clin. Invest.

Self Cite

103

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Recently the concept of using specific inhibitors of endogenous cholesterol synthesis as a means of reducing the cholesterol content of the body has been reviewed (1). One such specific inhibitor is the metal vanadium. Salts of vanadium have been shown to inhibit the utilization of mevalonic acid for cholesterol biosynthesis (2), to inhibit cholesterol biosynthesis in vitro and in vivo (3), to induce mobilization of predeposited aortic cholesterol in rabbits (4) and to lessen the deposition of cholesterol in rabbits (5) and in birds (6) fed high cholesterol diets.To extend these studies to man, the effects of vanadium on sterol balance in normocholesterolemic men under rigid dietary control were examined. The investigations reported here show that, under such conditions, inhibition of endogenous cholesterol biosynthesis with a salt of vanadium produces a lowering of serum cholesterol levels. The studies provide data which suggest that mobilization of tissue cholesterol stores also occurs. C. Experimental design. The men ate an identical diet during the entire study. After a two week control period, each man received diammonium oxy-tartratovanadate1 (B. B., 100 mg.; others, 125 mg.) orally in three divided doses each day for the experimental period of six weeks. During the final recovery period of three weeks the vanadium administration was discontinued.D. Chemical methods. Serum. Fasting blood samples were obtained once each week. Cholesterol (7), phospholipid (8, 9), triglyceride (10), alkaline phosphatase (11) and transaminase (12) serum levels were determined. Serum cholesterol determinations were carried out on duplicate aliquots of sera.Urine. Twenty-four hour samples were collected once each week and daily for the week after cessation of vanadium administration. Vanadium was determined by a colorimetric method (13) (20).Diet. Aliquots of the total 24 hour diet, prepared by homogenization in a Waring Blendor with water, were analyzed for total fat (20) and neutral sterol (7,16,17) content.

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“…Vanadium has been considered to have potential anti-hyperlipidemic effect. 2.5 mmol/L VOSO4·2H2O depressed the biosynthesis of cholesterol from labeled acetate in hepatic tissue of rats and the inhibition by vanadium occurred between the six and five carbon intermediates [11,19]. Vanadyl sulfate added in drinking water in the concentration of 0.2 mg/ml obviously lowered serum lipid value in streptozotocininduced hyperglycemic rats during a 29 days treatment [13].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

Wang

Jin

et al. 2014

Nutr Res Pract

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BACKGROUND:Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo TM ), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS: Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS: After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION: Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium.

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Site of Vanadium Inhibition of Cholesterol Biosynthesis

Cited by 42 publications

References 0 publications

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

Effect of Cholesterol Synthesis Inhibition in Normocholesteremic Young Men*

Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

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