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Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome

International Journal of Obesity volume 27, pages 862–865 (2003)Cite this article

Abstract

OBJECTIVE: We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome.

METHODS: A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n=13) (40 mg/day) or matching placebo (n=12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d3-leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol:cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively.

RESULTS: Compared with placebo, atorvastatin significantly decreased (P<0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol:cholesterol ratio decreased from 26.4±2.4 to 8.8±0.8, while the campesterol:cholesterol ratio increased from 26.5±4.4 to 38.6±5.8 (P<0.01). Atorvastatin also increased VLDL-apoB FCR from 3.82±0.33 to 6.30±0.75 pools/day (P<0.01), but did not significantly alter VLDL-apoB secretion (12.8±1.7 to 13.8±2.0 mg/kg/day).

CONCLUSIONS: In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL-apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.

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Acknowledgements

This study was supported by the National Heart Foundation of Australia, the National Health Medical Research Council of Australia, the Medical Research Foundation (Royal Perth Hospital), Pfizer Australia and the National Institutes of Health (NCRR 12609). PHRB is a Career Development Fellow of the National Heart Foundation.

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Authors and Affiliations

  1. School of Medicine and Pharmacology, University of Western Australia, West Australian Institute for Medical Research, Royal Perth Hospital, Perth, W Australia

    G F Watts, D C Chan & P H R Barrett

  2. Division of Investigative Science, Department of Metabolic Medicine, Imperial College School of Medicine, University of London, UK

    F H O' Neill & G R Thompson

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  1. G F Watts
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  2. D C Chan
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Correspondence to G F Watts.

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Watts, G., Chan, D., Barrett, P. et al. Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome. Int J Obes 27, 862–865 (2003). https://doi.org/10.1038/sj.ijo.0802287

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