Liraglutide Reduces Postprandial Hyperlipidemia by Increasing ApoB48 (Apolipoprotein B48) Catabolism and by Reducing ApoB48 Production in Patients With Type 2 Diabetes Mellitus
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Liraglutide significantly modifies lipoprotein metabolism, with an increase in chylomicron and LDL catabolism.
“Liraglutide has also been shown to significantly modify lipoprotein metabolism, with a reduction of chylomicron production [40, 41] and an increase in chylomicron and low-density lipoprotein (LDL) catabolism [40, 42].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [40]
GLP-1RAs markedly reduce postprandial increases in triglycerides, apolipoprotein B48, and apolipoprotein C-III, independently of gastric emptying.
“However, GLP-1RAs markedly reduced postprandial increases in triglycerides, apolipoprotein (Apo)B48 (major structural protein of chylomicrons), and ApoC-III (key regulator of triglyceride-rich lipoprotein metabolism), independently of gastric emptying [38–40].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [40]
In vitro studies showed that liraglutide directly reduced expression of several genes involved in chylomicron production and of the PCSK9 gene.
“In vitro studies further showed that liraglutide directly reduced the expression of several genes involved in chylomicron production and of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene [40, 42].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [40]
Liraglutide significantly modifies lipoprotein metabolism, with a reduction of chylomicron production.
“Liraglutide has also been shown to significantly modify lipoprotein metabolism, with a reduction of chylomicron production [40, 41] and an increase in chylomicron and low-density lipoprotein (LDL) catabolism [40, 42].”
From Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms (2022) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · see citing works
Nordestgaard, B. G., Benn, M., Schnohr, P., & Tybjærg-Hansen, A. (2007) · JAMA · doi:10.1001/jama.298.3.299 · Cited by 2,058 · see citing works
Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women
Bansal, S., Buring, J. E., Rifai, N., Mora, S., Sacks, F. M., & Ridker, P. M. (2007) · JAMA · doi:10.1001/jama.298.3.309 · Cited by 1,619 · see citing works
Astrup, A., Rössner, S., Van Gaal, L., Rissanen, A., Niskanen, L., Al Hakim, M., Madsen, J., Rasmussen, M. F., & Lean, M. E. (2009) · The Lancet · doi:10.1016/s0140-6736(09)61375-1 · Cited by 1,163 · see citing works
Pathophysiology of diabetic dyslipidaemia: where are we?
Vergès, B. (2015) · Diabetologia · doi:10.1007/s00125-015-3525-8 · Cited by 708 · see citing works
Self-citationNappo, F., Esposito, K., Cioffi, M., Giugliano, G., Molinari, A. M., Paolisso, G., Marfella, R., & Giugliano, D. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)01741-2 · Cited by 555 · see citing works
Nonfasting triglycerides and risk of ischemic stroke in the general population
Freiberg, J. J. (2008) · JAMA · doi:10.1001/jama.2008.621 · Cited by 542 · see citing works
GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting
Korner, M., Stockli, M., Waser, B., & Reubi, J. C. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.106.038679 · Cited by 477 · see citing works
Richards, P., Parker, H. E., Adriaenssens, A. E., Hodgson, J. M., Cork, S. C., Trapp, S., Gribble, F. M., & Reimann, F. (2014) · Diabetes · doi:10.2337/db13-1440 · Cited by 472 · see citing works
Duncan, G. E., Perri, M. G., Theriaque, D. W., Hutson, A. D., Eckel, R. H., & Stacpoole, P. W. (2003) · Diabetes Care · doi:10.2337/diacare.26.3.557 · Cited by 425 · see citing works
de Graaf, I. A. M., Olinga, P., de Jager, M. H., Merema, M. T., de Kanter, R., van de Kerkhof, E. G., & Groothuis, G. M. M. (2010) · Nature Protocols · doi:10.1038/nprot.2010.111 · Cited by 409 · see citing works
Meier, J. J., Gethmann, A., Götze, O., Gallwitz, B., Holst, J. J., Schmidt, W. E., & Nauck, M. A. (2006) · Diabetologia · doi:10.1007/s00125-005-0126-y · Cited by 276 · see citing works
Hsieh, J., Longuet, C., Baker, C. L., Qin, B., Federico, L. M., Drucker, D. J., & Adeli, K. (2009) · Diabetologia · doi:10.1007/s00125-009-1611-5 · Cited by 275 · see citing works
Schneeman, B. O., Kotite, L., Todd, K., & Havel, R. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.2069 · Cited by 255 · see citing works
Anderson, R. A., Evans, M. L., Ellis, G. R., Graham, J., Morris, K., Jackson, S. K., Lewis, M. J., Rees, A., & Frenneaux, M. P. (2001) · Atherosclerosis · doi:10.1016/s0021-9150(00)00499-8 · Cited by 248 · see citing works
Petit, J., Cercueil, J., Loffroy, R., Denimal, D., Bouillet, B., Fourmont, C., Chevallier, O., Duvillard, L., & Vergès, B. L. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2016-2775 · Cited by 228 · see citing works
Self-citationDuez, H., Lamarche, B., Uffelman, K. D., Valéro, R., Cohn, J. S., & Lewis, G. F. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000222015.76038.14 · Cited by 188 · see citing works
Karpe, F., & Hamsten, A. (1994) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)39974-0 · Cited by 182 · see citing works
Cobelli, C., TOFFOLO, G. M., & Foster, D. M. (1992) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1992.262.6.e968 · Cited by 177 · see citing works
Schwartz, E. A., Koska, J., Mullin, M. P., Syoufi, I., Schwenke, D. C., & Reaven, P. D. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.05.028 · Cited by 173 · see citing works
Xiao, C., Bandsma, R. H. J., Dash, S., Szeto, L., & Lewis, G. F. (2012) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.112.246207 · Cited by 164 · see citing works
Postprandial lipemia and cardiovascular disease
Hyson, D. A., Rutledge, J. C., & Berglund, L. (2003) · Current Atherosclerosis Reports · doi:10.1007/s11883-003-0033-y · Cited by 160 · see citing works
Increase of adipose tissue lipoprotein lipase activity with weight loss.
Schwartz, R. S., & Brunzell, J. D. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110171 · Cited by 153 · see citing works
Hermansen, K., Bækdal, T. A., Düring, M., Pietraszek, A., Mortensen, L. S., Jørgensen, H., & Flint, A. (2013) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12133 · Cited by 143 · see citing works
Hogue, J., Lamarche, B., Tremblay, A. J., Bergeron, J., Gagné, C., & Couture, P. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m600548-jlr200 · Cited by 127 · see citing works
Effect of Insulin Therapy on Metabolic Fate of Apolipoprotein B–Containing Lipoproteins in NIDDM
Taskinen, M., Packard, C. J., & Shepherd, J. (1990) · Diabetes · doi:10.2337/diab.39.9.1017 · Cited by 103 · see citing works
Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism
Lamon‐Fava, S., Diffenderfer, M. R., Barrett, P. H. R., Buchsbaum, A., Matthan, N. R., Lichtenstein, A. H., Dolnikowski, G. G., Horvath, K. V., Asztalos, B. F., Zago, V., et al. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700067-jlr200 · Cited by 80 · see citing works
Pont, F., Duvillard, L., Florentin, E., Gambert, P., & Vergès, B. L. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0802070 · Cited by 79 · see citing works
Self-citationCummings, M. H., Watts, G. F., Pal, C., Umpleby, A. M., Hennessy, T. R., Naoumova, R. P., & Sönksen, P. H. (1995) · Clinical Science · doi:10.1042/cs0880225 · Cited by 73 · see citing works
Adiels, M., Matikainen, N., Westerbacka, J., Söderlund, S., Larsson, T. P., Olofsson, S., Borén, J., & Taskinen, M. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.02.001 · Cited by 68 · see citing works
Degrace, P., Moindrot, B., Mohamed, I., Gresti, J., Du, Z., Chardigny, J., Sébédio, J., & Clouet, P. (2006) · Journal of Lipid Research · doi:10.1194/jlr.m600140-jlr200 · Cited by 68 · see citing works
Self-citationAtorvastatin Improves Postprandial Lipoprotein Metabolism in Normolipidemic Subjects1
Parhofer, K. G., Barrett, P. H. R., & SCHWANDT, P. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6978 · Cited by 65 · see citing works
Farr, S., Baker, C., Naples, M., Taher, J., Iqbal, J., Hussain, M. M., & Adeli, K. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304873 · Cited by 62 · see citing works
Shojaee‐Moradie, F., Ma, Y., Lou, S., Hovorka, R., & Umpleby, A. M. (2013) · Diabetes · doi:10.2337/db13-0935 · Cited by 59 · see citing works
Phillips, C. M., Mullan, K., Owens, D., & TOMKIN, G. H. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.08.020 · Cited by 52 · see citing works
Douglass, J. D., Malik, N., Chon, S., Wells, K., Zhou, Y. X., Choi, A. S., Joseph, L. B., & Storch, J. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00025 · Cited by 47 · see citing works
Duvillard, L., Pont, F., Florentin, E., Gambert, P., & Vergès, B. L. (2000) · Diabetologia · doi:10.1007/s001250050004 · Cited by 45 · see citing works
Self-citationPadilla, N., Maraninchi, M., Béliard, S., Berthet, B., Nogueira, J. P., Wolff, E., Nicolay, A., Corroller, A. B., Dubois, N., Grangeot, R., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.303849 · Cited by 43 · see citing works
Tsuchida, T., Fukuda, S., Aoyama, H., et al. (2012) · Lipids in Health and Disease · doi:10.1186/1476-511x-11-75 · Cited by 42 · see citing works
Kedees, M. H., Guz, Y., Grigoryan, M., & Teitelman, G. (2013) · Peptides · doi:10.1016/j.peptides.2013.07.022 · Cited by 35 · see citing works
Influence of Atorvastatin on Apolipoprotein E and AI Kinetics in Patients with Type 2 Diabetes
Bach‐Ngohou, K., Ouguerram, K., Frénais, R., Maugère, P., Piquer, B. R., Zaïr, Y., Krempf, M., & Bard, J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.085522 · Cited by 32 · see citing works
Effects of 20 mg rosuvastatin on VLDL1-, VLDL2-, IDL- and LDL-ApoB kinetics in type 2 diabetes
Vergès, B. L., Florentin, E., Baillot-Rudoni, S., Monier, S., Petit, J., Rageot, D., Gambert, P., & Duvillard, L. (2008) · Diabetologia · doi:10.1007/s00125-008-1046-4 · Cited by 26 · see citing works
Self-citationMore, V. R., Lao, J. Z., McLaren, D. G., Cumiskey, A.-M., Murphy, B. A., Chen, Y., Previs, S. F., Stout, S. J., Patel, R., Satapati, S., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186586 · Cited by 21 · see citing works
Tremblay, A. J., Lamarche, B., Ruel, I. L., Hogue, J., Deshaies, Y., Gagné, C., & Couture, P. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.10.037 · Cited by 13 · see citing works
Duvillard, L., Dautin, G., Florentin, E., Jeannin, A., de Barros, J.-P. P., Lagrost, L., Petit, J., Gambert, P., & Vergès, B. L. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1402 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Xiao C, Bandsma RHJ, Dash S, Szeto L, Lewis GF. Exenatide, a glu- cagon-like peptide-1 receptor agonist, acutely inhibits intestinal lipo- protein production in healthy humans. Arterioscler Thromb Vasc Biol. 2012;32:1513-1519. doi: 10.1161/ATVBAHA.112.246207 · DOI · Paper page
Cited by
Sorted by citations
The Discovery and Development of Liraglutide and Semaglutide
Knudsen, L. B., & Lau, J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00155 · Cited by 970 · see citing works
Metabolism of triglyceride-rich lipoproteins in health and dyslipidaemia
Borén, J., Taskinen, M.-R., Björnson, E., & Packard, C. J. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00676-y · Cited by 315 · see citing works
Causes and consequences of hypertriglyceridemia
Packard, C. J., Boren, J., & Taskinen, M.-R. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00252 · Cited by 239 · see citing works
Vergès, B., Aboyans, V., Angoulvant, D., Boutouyrie, P., Cariou, B., Hyafil, F., Mohammedi, K., & Amarenco, P. (2022) · Cardiovascular Diabetology · doi:10.1186/s12933-022-01686-3 · Cited by 72 · see citing works
Self-citationKolovou, G. D., Watts, G. F., Mikhailidis, D. P., Pérez-Martínez, P., Mora, S., Bilianou, H., Panotopoulos, G., Katsiki, N., Ooi, T. C., Lopez-Miranda, J., et al. (2019) · Current Vascular Pharmacology · doi:10.2174/1570161117666190507110519 · Cited by 61 · see citing works
Björnson, E., Packard, C. J., Adiels, M., Andersson, L., Matikainen, N., Söderlund, S., Kahri, J., Sihlbom, C., Thorsell, A., Zhou, H., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12877 · Cited by 54 · see citing works
Vergès, B., Duvillard, L., Pais de Barros, J. P., Bouillet, B., Baillot-Rudoni, S., Rouland, A., Petit, J. M., Degrace, P., & Demizieux, L. (2021) · Diabetes Care · doi:10.2337/dc20-1843 · Cited by 54 · see citing works
Self-citationBjörnson, E., Packard, C. J., Adiels, M., Andersson, L., Matikainen, N., Söderlund, S., Kahri, J., Hakkarainen, A., Lundbom, N., Lundbom, J., et al. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13017 · Cited by 46 · see citing works
Effects of liraglutide on the metabolism of triglyceride-rich lipoproteins in type 2 diabetes
Taskinen, M., Björnson, E., Matikainen, N., Söderlund, S., Pietiläinen, K. H., Ainola, M., Hakkarainen, A., Lundbom, N., Fuchs, J., Thorsell, A., et al. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14328 · Cited by 40 · see citing works
Effect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue: A meta-analysis
Berg, G., Barchuk, M., Lobo, M., & Nogueira, J. P. (2022) · Diabetes & Metabolic Syndrome: Clinical Research & Reviews · doi:10.1016/j.dsx.2022.102562 · Cited by 36 · see citing works
Lixisenatide Reduces Chylomicron Triacylglycerol by Increased Clearance
Whyte, M. B., Shojaee-Moradie, F., Sharaf, S. E., Jackson, N. C., Fielding, B., Hovorka, R., Mendis, J., Russell-Jones, D., & Umpleby, A. M. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01176 · Cited by 32 · see citing works
- Authors
- Vergès, B., Duvillard, L., Pais de Barros, J. P., Bouillet, B., Baillot-Rudoni, S., Rouland, A., Sberna, A.-L., Petit, J.-M., Degrace, P., & Demizieux, L.
- Affiliations
- Inserm (FR)
- INSERM LNR UMR1231, University of Burgundy and Franche-Comté, Dijon, France (B.V., L.D., J.P.P.d.B., B.B., J.-M.P., P.D., L.D.)
- From the Department of Endocrinology-Diabetology (B.V., B.B, S.B.-R., A.R., A.-L.S., J.M.P.)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2018-09
- Volume
- 38
- Issue
- 9
- Pages
- 2198-2206
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2884610847
- Cited by
- 75
- References
- 46
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 12 · 2020: 6 · 2019: 13 · 2018: 1
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-11-LABX-0021)
- Novo Nordisk
- Université de Bourgogne
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- liraglutide, apolipoprotein B-48, postprandial lipemia, type 2 diabetes, diabetic dyslipidemia, GLP-1 receptor agonists, DGAT1, microsomal triglyceride transfer protein, postprandial triglycerides, intestinal gene expression, serum lipoproteins, hepatic lipoprotein synthesis, hepatic lipoprotein secretion, hepatic lipoprotein uptake
- MeSH terms
- Liraglutide, Adipose Tissue, Animals, Carrier Proteins, Chylomicrons, Diabetes Mellitus, Type 2, Female, Humans, Hyperlipidemias, Jejunum, Lipoprotein Lipase, Male, Mice, Inbred BALB C, Prospective Studies, Triglycerides, Gene Expression, Postprandial Period, Diacylglycerol O-Acyltransferase, Apolipoprotein B-48
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
