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PSD3 downregulation confers protection against fatty liver disease.

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
Sasidharan, Kavitha (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Lindblom, Anna (author)
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Wei, Ying (author)
Ciociola, Ester (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Oveis, Jamialahmadi (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Pingitore, Piero, 1986 (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Andréasson, Anne-Christine (author)
Pellegrini, Giovanni (author)
Baselli, Guido (author)
Männistö, Ville (author)
Pihlajamäki, Jussi (author)
Kärjä, Vesa (author)
Grimaudo, Stefania (author)
Marini, Ilaria (author)
Maggioni, Marco (author)
Becattini, Barbara (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Tavaglione, Federica (author)
Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
Dix, Carly (author)
Castaldo, Marie (author)
Klein, Stephanie (author)
Perelis, Mark (author)
Pattou, Francois (author)
Thuillier, Dorothée (author)
Raverdy, Violeta (author)
Dongiovanni, Paola (author)
Fracanzani, Anna Ludovica (author)
Stickel, Felix (author)
Hampe, Jochen (author)
Buch, Stephan (author)
Luukkonen, Panu K (author)
Prati, Daniele (author)
Yki-Järvinen, Hannele (author)
Petta, Salvatore (author)
Xing, Chao (author)
Schafmayer, Clemens (author)
Aigner, Elmar (author)
Datz, Christian (author)
Lee, Richard G (author)
Valenti, Luca (author)
Lindén, Daniel (author)
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
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 (creator_code:org_t)
2022-01-31
2022
English.
In: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 4:1, s. 60-75
Related links:
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https://gup.ub.gu.se...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cells. Consistent with this, Psd3 downregulation by antisense oligonucleotides in vivo protects against FLD in mice fed a non-alcoholic steatohepatitis-inducing diet. Thus, translating these results to humans, PSD3 downregulation might be a future therapeutic option for treating FLD.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

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art (subject category)

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