Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus

Autor: Laurent Demizieux, Jean Paul Pais de Barros, Jean-Michel Petit, Benjamin Bouillet, S. Baillot-Rudoni, Alexia Rouland, Laurence Duvillard, Pascal Degrace, Bruno Vergès, Anne-Laure Sberna
Přispěvatelé: université de Bourgogne, LNC, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Biochimie [CHU de Dijon]
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
Apolipoprotein B-48
Agonist
medicine.medical_specialty
medicine.drug_class
hyperlipidemias
Gene Expression
030209 endocrinology & metabolism
030204 cardiovascular system & hematology
patients
03 medical and health sciences
0302 clinical medicine
Internal medicine
Diabetes mellitus
Chylomicrons
Hyperlipidemia
Animals
Humans
Medicine
Diacylglycerol O-Acyltransferase
Prospective Studies
Triglycerides
[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Mice
Inbred BALB C
liraglutide
business.industry
Liraglutide
Catabolism
Type 2 Diabetes Mellitus
[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Postprandial Period
medicine.disease
Lipoprotein Lipase
Jejunum
Endocrinology
Postprandial
Adipose Tissue
Diabetes Mellitus
Type 2
kinetics
diabetes mellitus
Female
Carrier Proteins
Cardiology and Cardiovascular Medicine
business
medicine.drug
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2018, 38, pp.2198-2206. ⟨10.1161/ATVBAHA.118.310990⟩
ISSN: 1079-5642
1524-4636
DOI: 10.1161/ATVBAHA.118.310990⟩
Popis: Objective— Treatment with liraglutide, a GLP-1 (glucagon-like peptide-1) agonist, has been shown to reduce postprandial lipidemia, an important feature of diabetic dyslipidemia. However, the underlying mechanisms for this effect remain unknown. This prompted us to study the effect of liraglutide on the metabolism of ApoB48 (apolipoprotein B48). Approach and Results— We performed an in vivo kinetic study with stable isotopes (D 8 -valine) in the fed state in 10 patients with type 2 diabetes mellitus before treatment and 6 months after the initiation of treatment with liraglutide (1.2 mg/d). We also evaluated, in mice, the effect of a 1-week liraglutide treatment on postload triglycerides and analysed in vitro on jejunum, the direct effect of liraglutide on the expression of genes involved in the biosynthesis of chylomicron. In diabetic patients, liraglutide treatment induced a dramatic reduction of ApoB48 pool (65±38 versus 162±87 mg; P =0.005) because of a significant decrease in ApoB48 production rate (3.02±1.33 versus 6.14±4.27 mg kg -1 d -1 ; P =0.009) and a significant increase in ApoB48 fractional catabolic rate (5.12±1.35 versus 3.69±0.75 pool d -1 ; P =0.005). One-week treatment with liraglutide significantly reduced postload plasma triglycerides in mice and liraglutide, in vitro, reduced the expression of ApoB48, DGAT1 (diacylglycerol O-acyltransferase 1), and MTP (microsomal transfer protein) genes. Conclusions— We show that treatment with liraglutide induces a significant reduction of the ApoB48 pool because of both a reduction of ApoB48 production and an increase in ApoB48 catabolism. In vitro, liraglutide reduces the expression of genes involved in chylomicron synthesis. These effects might benefit cardiovascular health. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02721888.
Databáze: OpenAIRE
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