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Paradoxical Dissoci...
Paradoxical Dissociation Between Hepatic Fat Content and De Novo Lipogenesis Due to PNPLA3 Sequence Variant
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- Mancina, Rosellina Margherita (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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Matikainen, N. (author)
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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
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Soderlund, S. (author)
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Lundbom, N. (author)
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Hakkarainen, A. (author)
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Rametta, R. (author)
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Mozzi, E. (author)
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Fargion, S. (author)
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Valenti, L. (author)
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- Romeo, Stefano, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberglaboratoriet,Institute of Medicine, Department of Molecular and Clinical Medicine,Wallenberg Laboratory
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Taskinen, M. R. (author)
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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
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(creator_code:org_t)
- The Endocrine Society, 2015
- 2015
- English.
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In: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:5
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Context: Nonalcoholic fatty liver disease (NAFLD) is an emerging epidemic disease characterized by increased hepatic fat, due to an imbalance between synthesis and removal of hepatic lipids. In particular, increased hepatic de novo lipogenesis (DNL) is a key feature associated with NAFLD. The genetic variations I148M in PNPLA3 and E167K in TM6SF2 confer susceptibility to NAFLD. Objective: Here we aimed to investigate the contribution of DNL to liver fat accumulation in the PNPLA3 I148M or TM6SF2 E167K genetic determinants of NAFLD. Patients and Methods: The PNPLA3 I148M and TM6SF2 E167K were genotyped in two well-characterized cohorts of Europeans. In the first cohort (Helsinki cohort; n = 88), we directly quantified hepatic DNL using deuterated water. In the second cohort (Milan cohort; n = 63), we quantified the hepatic expression of SREBP1c that we have found previously associated with increased fat content. Liver fat was measured by magnetic resonance proton spectroscopy in the Helsinki cohort, and by histological assessment of liver biopsies in the Milan cohort. Results: PNPLA3 148M was associated with lower DNL and expression of the lipogenic transcription factor SREBP1c despite substantial increased hepatic fat content. Conclusions: Our data show a paradoxical dissociation between hepatic DNL and hepatic fat content due to the PNPLA3 148M allele indicating that increased DNL is not a key feature in all individuals with hepatic steatosis, and reinforces the contribution of decreased mobilization of hepatic triglycerides for hepatic lipid accumulation in subject with the PNPLA3 148M allele.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- SUPERFAMILY MEMBER 2
- LIVER-DISEASE
- NONALCOHOLIC STEATOHEPATITIS
- HEPATOCELLULAR-CARCINOMA
- CONFERS SUSCEPTIBILITY
- GENETIC-VARIATION
- NATURAL-HISTORY
- TM6SF2
- INDIVIDUALS
- EXPRESSION
- Endocrinology & Metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Mancina, Roselli ...
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Matikainen, N.
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Maglio, Cristina ...
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Soderlund, S.
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Lundbom, N.
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Hakkarainen, A.
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show more...
-
Rametta, R.
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Mozzi, E.
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Fargion, S.
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Valenti, L.
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Romeo, Stefano, ...
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Taskinen, M. R.
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Borén, Jan, 1963
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show less...
- 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 Endocrinology an ...
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Journal of Clini ...
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University of Gothenburg