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  • Taskinen, M. R. (author)

Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-10-10
  • American Society for Clinical Investigation,2022

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/320868
  • https://gup.ub.gu.se/publication/320868URI
  • https://doi.org/10.1172/jci.insight.160607DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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)
  • Matikainen, N. (author)
  • Soderlund, S. (author)
  • Ramo, J. (author)
  • Ainola, M. M. (author)
  • Hakkarainen, A. (author)
  • Sihlbom, C. (author)
  • Thorsell, A. (author)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Ripatti, S. (author)
  • Laakso, M. (author)
  • Packard, C. J. (author)
  • 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)
  • Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)

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  • In:Jci Insight: American Society for Clinical Investigation7:192379-3708

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