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Suppression of insu...
Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression
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Azzu, V. (författare)
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Vacca, M. (författare)
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Kamzolas, I. (författare)
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visa fler...
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Hall, Z. (författare)
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Leslie, J. (författare)
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Carobbio, S. (författare)
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Virtue, S. (författare)
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Davies, S. E. (författare)
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Lukasik, A. (författare)
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Dale, M. (författare)
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Bohlooly-Y, M. (författare)
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Acharjee, A. (författare)
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- Lindén, Daniel, 1971 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Bidault, G. (författare)
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Petsalaki, E. (författare)
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Griffin, J. L. (författare)
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Oakley, F. (författare)
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Allison, M. E. D. (författare)
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Vidal-Puig, A. (författare)
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- Engelska.
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 48
- Relaterad länk:
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Objective: Non-alcoholic fatty liver disease (NAFLD) is a silent pandemic associated with obesity and the metabolic syndrome, and also increases cardiovascular- and cirrhosis-related morbidity and mortality. A complete understanding of adaptive compensatory metabolic programmes that modulate non-alcoholic steatohepatitis (NASH) progression is lacking. Methods and results: Transcriptomic analysis of liver biopsies in patients with NASH revealed that NASH progression is associated with rewiring of metabolic pathways, including upregulation of de novo lipid/cholesterol synthesis and fatty acid remodelling. The modulation of these metabolic programmes was achieved by activating sterol regulatory element-binding protein (SREBP) transcriptional networks; however, it is still debated whether, in the context of NASH, activation of SREBPs acts as a pathogenic driver of lipotoxicity, or rather promotes the biosynthesis of protective lipids that buffer excessive lipid accumulation, preventing inflammation and fibrosis. To elucidate the pathophysiological role of SCAP/SREBP in NASH and wound-healing response, we used an Insig1 deficient (with hyper-efficient SREBPs) murine model challenged with a NASH-inducing diet. Despite enhanced lipid and cholesterol biosynthesis, Insig1 KO mice had similar systemic metabolism and insulin sensitivity to Het/WT littermates. Moreover, activating SREBPs resulted in remodelling the lipidome, decreased hepatocellular damage, and improved wound-healing responses. Conclusions: Our study provides actionable knowledge about the pathways and mechanisms involved in NAFLD pathogenesis, which may prove useful for developing new therapeutic strategies. Our results also suggest that the SCAP/SREBP/INSIG1 trio governs transcriptional programmes aimed at protecting the liver from lipotoxic insults in NASH. (C) 2021 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- Non-alcoholic fatty liver disease (NAFLD)
- De novo lipogenesis (DNL)
- Lipid remodelling
- Western diet
- Carbon tetrachloride (CCl4)
- Liver
- regeneration
- fatty liver-disease
- de-novo lipogenesis
- nonalcoholic steatohepatitis
- free-cholesterol
- scoring system
- mice
- metabolism
- expression
- resistance
- steatosis
- Endocrinology & Metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Azzu, V.
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Vacca, M.
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Kamzolas, I.
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Hall, Z.
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Leslie, J.
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Carobbio, S.
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visa fler...
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Virtue, S.
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Davies, S. E.
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Lukasik, A.
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Dale, M.
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Bohlooly-Y, M.
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Acharjee, A.
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Lindén, Daniel, ...
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Bidault, G.
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Petsalaki, E.
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Griffin, J. L.
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Oakley, F.
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Allison, M. E. D ...
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Vidal-Puig, A.
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Neurovetenskaper
- Artiklar i publikationen
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Molecular Metabo ...
- Av lärosätet
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Göteborgs universitet