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The PNPLA3 I148M va...
The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
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- Luukkonen, Panu K. (författare)
- Minerva Foundation Institute for Medical Research,Helsinki University Central Hospital,Yale University,University of Helsinki
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- Porthan, Kimmo (författare)
- Minerva Foundation Institute for Medical Research,University of Helsinki
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- Ahlholm, Noora (författare)
- Minerva Foundation Institute for Medical Research,University of Helsinki
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- Rosqvist, Fredrik, 1985- (författare)
- Uppsala University,Uppsala universitet,Klinisk nutrition och metabolism,Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford & NIHR Oxford Biomedical Research Centre, Oxford University Hospitals Foundation Trust, Oxford, UK
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- Dufour, Sylvie (författare)
- Yale University
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- Zhang, Xian-Man (författare)
- Yale University
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- Lehtimäki, Tiina E. (författare)
- University of Helsinki
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- Seppänen, Wenla (författare)
- University of Helsinki
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- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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Hodson, Leanne (författare)
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- Petersen, Kitt Falk (författare)
- Yale University
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- Shulman, Gerald I. (författare)
- Yale University
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- Yki-Järvinen, Hannele (författare)
- University of Helsinki,Minerva Foundation Institute for Medical Research
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(creator_code:org_t)
- Elsevier, 2023
- 2023
- Engelska.
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Ingår i: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 35:11, s. 1887-1896.e5
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma b-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty acids were channeled toward ketogenesis in carriers, which was associated with an increase in hepatic mitochondrial redox state. During a ketogenic diet, carriers manifested increased rates of intrahepatic lipolysis, increased plasma b-hydroxybutyrate concentrations, and decreased rates of hepatic mitochondrial citrate synthase flux. These studies demonstrate that homozygous PNPLA3 I148M carriers have hepatic mitochondrial dysfunction leading to reduced DNL and channeling of carbons to ketogenesis. These findings have implications for understanding why the PNPLA3 variant predisposes to progressive liver disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Nyckelord
- patatin-like phospholipase domain containing protein 3
- NAFLD
- NASH
- redox
- GDF-15
- mitochondrial dysfunction
- ketogenic diet
- reductive stress
- NADH
- NAD
- GDF-15
- ketogenic diet
- mitochondrial dysfunction
- NAD
- NADH
- NAFLD
- NASH
- patatin-like phospholipase domain containing protein 3
- redox
- reductive stress
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- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Luukkonen, Panu ...
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Porthan, Kimmo
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Ahlholm, Noora
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Rosqvist, Fredri ...
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Dufour, Sylvie
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Zhang, Xian-Man
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visa fler...
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Lehtimäki, Tiina ...
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Seppänen, Wenla
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Orho-Melander, M ...
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Hodson, Leanne
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Petersen, Kitt F ...
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Shulman, Gerald ...
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Yki-Järvinen, Ha ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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och Klinisk medicin
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Cell Metabolism
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Uppsala universitet
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