Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes

Ouguerram, Khadija; Magot, Thierry; Zäir, Yassine; Marchini, J.S.; Charbonnel, Bernard; Laouenan, Herve; Krempf, Michel

doi:10.1124/jpet.103.048991

Cited by 44Lipoproteins and Cardiovascular HealthLipid metabolism and disordersCholesterol and Lipid Metabolism

Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes

Ouguerram, Khadija, Magot, Thierry, Zäir, Yassine, Marchini, J.S., Charbonnel, Bernard, Laouenan, Herve, Krempf, Michel·2003·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1124/jpet.103.048991

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Abstract

Seven hypertriglyceridemic patients with type-2 diabetes were treated with atorvastatin (40 mg/day) for 2 months. Kinetics of apolipoprotein B100 (apoB100)-containing lipoproteins were determined before and after atorvastatin treatment and compared with data obtained in five normolipidemic volunteers. ApoB100 metabolism was studied using stable isotopes and multicompartmental modeling. Compared with normolipidemic obese subjects, type-2 diabetic patients had a higher apoB100 concentration in very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL) (P < 0.005). Kinetic analysis showed an increase in the total apoB100 production rate (P < 0.005) related to VLDL apoB100 overproduction (P < 0.005). Patients were also characterized by a lower fractional catabolic rate (FCR) in VLDL (not significant) or IDL (P < 0.005) mainly related to a decrease in VLDL and IDL delipidation rate (P < 0.005). Catabolism of LDL was also lower in diabetic patients (P < 0.05). Atorvastatin treatment significantly decreased plasma triglycerides (P < 0.05), total and LDL cholesterol (P < 0.05), apoB100 in LDL, IDL, and VLDL (P < 0.05). Treatment significantly decreased total apoB100 production rate (P < 0.05), but only for VLDL (P < 0.05). Treatment normalized FCR in IDL and LDL (P < 0.05). We concluded that atorvastatin improved lipid abnormalities in type-2 diabetic patients not only by increasing the clearance of apoB100-containing lipoproteins but also by decreasing VLDL production.

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The increased VLDL and IDL pool for the HC126 patient was also due to an increased production rate, not observed for E2E2 patients, but already reported for patients carrying a PCSK9 gene mutation.
“Interestingly, the increased VLDL and IDL pool for the HC126 patient was also due to an increased production rate, that was not observed for E2E2 patients, but already reported for patients carrying a PCSK9 gene mutation (Ouguerram K et al. 2003).”
From Description of a Large Family with Autosomal Dominant Hypercholesterolemia Associated with theAPOEp.Leu167del Mutation (2013) · cites this paper as Ouguerram K et al. 2003

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Authors: Ouguerram, K., Magot, T., Zäir, Y., Marchini, J. S., Charbonnel, B., Laouenan, H., & Krempf, M.
Affiliations: Inserm (FR)
ORCID: Ouguerram, Khadija
Marchini, J.S.
Charbonnel, Bernard
Krempf, Michel
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 2003-07
Volume: 306
Issue: 1
Pages: 332-337
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1124/jpet.103.048991
OpenAlex: W2111895850
Cited by: 44
References: 42
Citations by year: 2023: 1 · 2021: 1 · 2017: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 2
FWCI: 4.39
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords: atorvastatin, apolipoprotein B-100, lipoprotein metabolism, type 2 diabetes, hypertriglyceridemia, fractional catabolic rate, delipidation, LDL catabolism, IDL, plasma triglycerides, cholesterol lowering, statin therapy
MeSH terms: Atorvastatin, Adult, Aged, Anticholesteremic Agents, Apolipoproteins B, Diabetes Mellitus, Type 2, Female, Heptanoic Acids, Humans, Kinetics, Lipoproteins, Lipoproteins, LDL, Lipoproteins, VLDL, Male, Middle Aged, Pyrroles, Lipid Metabolism, Apolipoprotein B-100

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Effect of atorvastatin on apolipoprotein B100 containing lipoprotein metabolism in type-2 diabetes

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