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Patatin-like phosph...
Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) affects hepatic VLDL secretion in humans and in vitro
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- Pirazzi, Carlo (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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- Adiels, Martin, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institutionen för matematiska vetenskaper,Institute of Medicine, Department of Molecular and Clinical Medicine,Department of Mathematical Sciences,University of Gothenburg,Chalmers tekniska högskola,Chalmers University of Technology
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- Burza, Maria Antonella, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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- Mancina, Rosellina Margherita (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory,University of Gothenburg
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- Levin, Malin, 1973 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Wallenberg Laboratory
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- Ståhlman, Marcus, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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Taskinen, M. R. (author)
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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- Perman, Jeanna, 1981 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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Pujia, A. (author)
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- Andersson, Linda, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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- Maglio, Cristina, 1983 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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Montalcini, T. (author)
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- Wiklund, Olov, 1943 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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- Borén, Jan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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- Romeo, Stefano, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,University of Gothenburg
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- Levin, Max, 1969 (author)
- Göteborgs universitet,University of Gothenburg
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(creator_code:org_t)
- Elsevier BV, 2012
- 2012
- English.
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In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 57:6, s. 1276-1282
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Abstract
Subject headings
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- Background & Aims: The robust association between non-alcoholic fatty liver disease (NAFLD) and the genetic variant I148M (rs738409) in PNPLA3 has been widely replicated. The aim of this study was to investigate the effect of the PNPLA3 I148M mutation on: (1) hepatic secretion of very low density lipoproteins (VLDL) in humans; and (2) secretion of apolipoprotein B (apoB) from McA-RH 7777 cells, which secrete VLDL-sized apoB-containing lipoproteins. Methods: VLDL kinetics was analyzed after a bolus infusion of stable isotopes in 55 overweight/obese men genotyped for the PNPLA3 I148M variant. Intracellular lipid content, apoB secretion and glycerolipid metabolism were studied in McA-RH 7777 cells overexpressing the human 1481 wild type or 148M mutant PNPLA3 protein. Results: In humans, carriers of the PNPLA3 148M allele had increased liver fat compared to 1481 homozygotes, and kinetic analysis showed a relatively lower secretion of the large, triglyceride-rich VLDL (VLDL1) in 148M carriers vs. 1481 homozygotes for the same amount of liver fat. McA-RH 7777 cells overexpressing the 148M mutant protein showed a higher intracellular triglyceride content with a lower apoB secretion and fatty acid efflux, compared to cells overexpressing the 1481 wild type protein. The responses with 148M matched those observed in cells expressing the empty vector, indicating that the mutation results in loss of function. Conclusions: We have shown that PNPLA3 affects the secretion of apoB-containing lipoproteins both in humans and in vitro and that the 148M protein is a loss-of-function mutation. We propose that PNPLA3 148M promotes intracellular lipid accumulation in the liver by reducing the lipidation of VLDL.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- Genetic variant
- Patatin-like phospholipase domain-containing 3
- Liver fat content
- VLDL secretion
- fatty liver-disease
- low-density lipoprotein
- b-containing lipoproteins
- apolipoprotein-b
- triglyceride hydrolysis
- obese subjects
- cell-line
- triacylglycerol
- adiponutrin
- hypobetalipoproteinemia
- Patatin-like phospholipase domain-containing 3
- Liver
- fat content
- Apolipoprotein B
- Lipolysis
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Pirazzi, Carlo
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Adiels, Martin, ...
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Burza, Maria Ant ...
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Mancina, Roselli ...
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Levin, Malin, 19 ...
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Ståhlman, Marcus ...
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show more...
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Taskinen, M. R.
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Orho-Melander, M ...
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Perman, Jeanna, ...
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Pujia, A.
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Andersson, Linda ...
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Maglio, Cristina ...
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Montalcini, T.
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Wiklund, Olov, 1 ...
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Borén, Jan, 1963
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Romeo, Stefano, ...
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Levin, Max, 1969
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Gastroenterology ...
- Articles in the publication
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Journal of Hepat ...
- By the university
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University of Gothenburg
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Chalmers University of Technology
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Lund University