Sökning: onr:"swepub:oai:gup.ub.gu.se/202198" > PNPLA3 has retinyl-...
Fältnamn | Indikatorer | Metadata |
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000 | 06751naa a2200697 4500 | |
001 | oai:gup.ub.gu.se/202198 | |
003 | SwePub | |
008 | 240528s2014 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/2021982 URI |
024 | 7 | a https://doi.org/10.1093/hmg/ddu1212 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Pirazzi, Carlou Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xpirca |
245 | 1 0 | a PNPLA3 has retinyl-palmitate lipase activity in human hepatic stellate cells |
264 | c 2014-03-25 | |
264 | 1 | b Oxford University Press (OUP),c 2014 |
520 | a Retinoids are micronutrients that are stored as retinyl esters in the retina and hepatic stellate cells (HSCs). HSCs are key players in fibrogenesis in chronic liver diseases. The enzyme responsible for hydrolysis and release of retinyl esters from HSCs is unknown and the relationship between retinoid metabolism and liver disease remains unclear. We hypothesize that the patatin-like phospholipase domain-containing 3 (PNPLA3) protein is involved in retinol metabolism in HSCs. We tested our hypothesis both in primary human HSCs and in a human cohort of subjects with non-alcoholic fatty liver disease (N = 146). Here we show that PNPLA3 is highly expressed in human HSCs. Its expression is regulated by retinol availability and insulin, and increased PNPLA3 expression results in reduced lipid droplet content. PNPLA3 promotes extracellular release of retinol from HSCs in response to insulin. We also show that purified wild-type PNPLA3 hydrolyzes retinyl palmitate into retinol and palmitic acid. Conversely, this enzymatic activity is markedly reduced with purified PNPLA3 148M, a common mutation robustly associated with liver fibrosis and hepatocellular carcinoma development. We also find the PNPLA3 I148M genotype to be an independent (P = 0.009 in a multivariate analysis) determinant of circulating retinol-binding protein 4, a reliable proxy for retinol levels in humans. This study identifies PNPLA3 as a lipase responsible for retinyl-palmitate hydrolysis in HSCs in humans. Importantly, this indicates a potential novel link between HSCs, retinoid metabolism and PNPLA3 in determining the susceptibility to chronic liver disease. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicin0 (SwePub)3022 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicine0 (SwePub)3022 hsv//eng |
653 | a FATTY LIVER-DISEASE | |
653 | a TRIGLYCERIDE HYDROLASE ACTIVITY | |
653 | a 2ND PRIMARY | |
653 | a TUMORS | |
653 | a HEPATOCELLULAR-CARCINOMA | |
653 | a I148M RS738409 | |
653 | a RAT-LIVER | |
653 | a PICHIA-PASTORIS | |
653 | a GENETIC VARIANT | |
653 | a VITAMIN-A | |
653 | a PREVENTION | |
653 | a Biochemistry & Molecular Biology | |
653 | a Genetics & Heredity | |
700 | 1 | a Valenti, L.4 aut |
700 | 1 | a Motta, Benedetta Mariau Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut |
700 | 1 | a Pingitore, Piero,d 1986u Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology4 aut0 (Swepub:gu)xpinpi |
700 | 1 | a Hedfalk, Kristina,d 1969u Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology4 aut0 (Swepub:gu)xhedkr |
700 | 1 | a Mancina, Rosellina Margheritau Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xmanro |
700 | 1 | a Burza, Maria Antonella,d 1980u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xburzm |
700 | 1 | a Indiveri, C.4 aut |
700 | 1 | a Ferro, Y.4 aut |
700 | 1 | a Montalcini, T.4 aut |
700 | 1 | a Maglio, Cristina,d 1983u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xmagcr |
700 | 1 | a Dongiovanni, P.4 aut |
700 | 1 | a Fargion, S.4 aut |
700 | 1 | a Rametta, R.4 aut |
700 | 1 | a Pujia, A.4 aut |
700 | 1 | a Andersson, Linda,d 1973u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xanlin |
700 | 1 | a Ghosal, Saswatiu Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut |
700 | 1 | a Levin, Malin,d 1973u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xlevim |
700 | 1 | a Wiklund, Olov,d 1943u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xwikol |
700 | 1 | a Iacovino, M.4 aut |
700 | 1 | a Borén, Jan,d 1963u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xborej |
700 | 1 | a Romeo, Stefano,d 1976u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xroste |
710 | 2 | a Göteborgs universitetb Institutionen för medicin, avdelningen för molekylär och klinisk medicin4 org |
773 | 0 | t Human Molecular Geneticsd : Oxford University Press (OUP)g 23:15, s. 4077-4085q 23:15<4077-4085x 0964-6906x 1460-2083 |
856 | 4 | u https://academic.oup.com/hmg/article-pdf/23/15/4077/17260502/ddu121.pdf |
856 | 4 8 | u https://gup.ub.gu.se/publication/202198 |
856 | 4 8 | u https://doi.org/10.1093/hmg/ddu121 |
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