Hepatic Hydroxymethylglutaryl Coenzyme A Reductase
Activity in Inbred Strains of Mice

Dupont, Jacqueline; Aubert, Roberte; Kuan, Son-Iu; Warner, David S.; Camus, Marie-Claire; Herzog, Jeannine

doi:10.1159/000469163

Enzyme

1988

DOI: 10.1159/000469163

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Hepatic Hydroxymethylglutaryl Coenzyme A Reductase Activity in Inbred Strains of Mice

Jacqueline Dupont¹,

Roberte Aubert²,

Son-Iu Kuan³

et al.

Abstract: Hydroxymethylglutaryl coenzyme A reductase (HMGR) activity is a major factor in the regulation of cholesterol homeostasis. Enzyme activity is known to vary with age, sex, diurnal cycle, and dietary properties in rats. Mice are available in numerous genetic strains and could be a useful inexpensive animal model for studying diet and genetic interactions in the regulation of cholesterol metabolism. Obese and non-obese C57BL/6J, CBA/J, and obese and non-obese DW db^Pas mice were subjected to variations in light c… Show more

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2006

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Cited by 2 publications

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Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Kojima

Degawa

2006

J. Appl. Toxicol.

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Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats.

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Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Kojima

Degawa

2006

J. Appl. Toxicol.

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Dietary Fat and Cholesterol Effects on Cholesterol Metabolism in CBA/J and C57BR/cdJ Mice

Kuan

Dupont

1989

The Journal of Nutrition

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The aim of this study was to determine how small differences in dietary fats affect cholesterol metabolism in mice hypo- (CBA/J) and hyperresponsive (C57BR/cdJ) to diet-induced hypercholesterolemia. Six-wk-old male mice were fed either a diet corresponding to the U.S. average gross composition (US74, 40% of total energy as fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) or a modified-fat diet (30% of total energy as fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91). After 8 wk of feeding, neither strain had developed hypercholesterolemia. CBA/J mice had higher concentrations of serum total and high-density lipoprotein (HDL) cholesterol and a higher esterified-to-free cholesterol ratio than did C57BR/cdJ mice. CBA/J mice maintained a constant serum cholesterol concentration mainly by adjusting the hepatic hydroxymethylglutaryl coenzyme A reductase (HMGR) activity, whereas C57BR/cdJ mice did so by changing the fecal excretion of cholesterol. Compared to the modified-fat diet, the US74 diet caused an increase in the ratio of total to HDL serum cholesterol, liver microsomal free cholesterol, fecal cholesterol and hepatic microsomal cholesterol 7 alpha-hydroxylase activity and a decrease in hepatic microsomal HMGR activity. We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice.

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Hepatic Hydroxymethylglutaryl Coenzyme A Reductase Activity in Inbred Strains of Mice

Cited by 2 publications

References 11 publications

Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Dietary Fat and Cholesterol Effects on Cholesterol Metabolism in CBA/J and C57BR/cdJ Mice

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