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Postprandial metabo...
Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-10-10
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American Society for Clinical Investigation,2022
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LIBRIS-ID:oai:gup.ub.gu.se/320868
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https://gup.ub.gu.se/publication/320868URI
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https://doi.org/10.1172/jci.insight.160607DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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BACKGROUND. Apolipoprotein C-III (apoC-III) is a regulator of triglyceride (TG) metabolism, and due to its association with risk of cardiovascular disease, is an emergent target for pharmacological intervention. The impact of substantially lowering apoC-III on lipoprotein metabolism is not clear.METHODS. We investigated the kinetics of apolipoproteins B48 and B100 (apoB48 and apoB100) in chylomicrons, VLDL1, VLDL2, IDL, and LDL in patients heterozygous for a loss-of-function (LOF) mutation in the APOC3 gene. Studies were conducted in the postprandial state to provide a more comprehensive view of the influence of this protein on TG transport.RESULTS. Compared with non-LOF variant participants, a genetically determined decrease in apoC-III resulted in marked acceleration of lipolysis of TG-rich lipoproteins (TRLs), increased removal of VLDL remnants from the bloodstream, and substantial decrease in circulating levels of VLDL1, VLDL2, and IDL particles. Production rates for apoB48-containing chylomicrons and apoB100-containing VLDL1 and VLDL2 were not different between LOF carriers and noncarriers. Likewise, the rate of production of LDL was not affected by the lower apoC-III level, nor were the concentration and clearance rate of LDL-apoB100.CONCLUSION. These findings indicate that apoC-III lowering will have a marked effect on TRL and remnant metabolism, with possibly significant consequences for cardiovascular disease prevention. TRIAL REGISTRATION. ClinicalTrials.gov NCT04209816 and NCT01445730.
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Björnson, Elias,1988Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbelia
(author)
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Matikainen, N.
(author)
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Soderlund, S.
(author)
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Ramo, J.
(author)
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Ainola, M. M.
(author)
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Hakkarainen, A.
(author)
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Sihlbom, C.
(author)
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Thorsell, A.
(author)
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Andersson, Linda,1973Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xanlin
(author)
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Bergh, Per-OlofGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbpero
(author)
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Henricsson, Marcus,1975Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xstahm
(author)
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Romeo, Stefano,1976Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xroste
(author)
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Adiels, Martin,1976Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xadima
(author)
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Ripatti, S.
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Laakso, M.
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Packard, C. J.
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Borén, Jan,1963Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xborej
(author)
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Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin
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In:Jci Insight: American Society for Clinical Investigation7:192379-3708
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Taskinen, M. R.
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Björnson, Elias, ...
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Matikainen, N.
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Soderlund, S.
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Ramo, J.
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Ainola, M. M.
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Hakkarainen, A.
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Sihlbom, C.
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Thorsell, A.
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Andersson, Linda ...
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Bergh, Per-Olof
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Henricsson, Marc ...
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Romeo, Stefano, ...
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Adiels, Martin, ...
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Ripatti, S.
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Laakso, M.
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Packard, C. J.
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Borén, Jan, 1963
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