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Macrophage scavenge...
Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease
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- Govaere, O. (author)
- Newcastle Univ, England
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- Petersen, S. K. (author)
- Univ Gothenburg, Sweden
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- Martinez-Lopez, N. (author)
- Albert Einstein Coll Med, NY 10461 USA; Albert Einstein Coll Med, NY 10461 USA
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- Wouters, J. (author)
- VIB KU Leuven, Belgium; Katholieke Univ Leuven, Belgium
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- Van Haele, M. (author)
- Katholieke Univ Leuven, Belgium; Univ Hosp Leuven, Belgium
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- Mancina, Rosellina Margherita (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine,Univ Gothenburg, Sweden
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- 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,Univ Gothenburg, Sweden
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- Bilkei-Gorzo, O. (author)
- Univ Gothenburg, Sweden
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- Lassen, P. B. (author)
- Sorbonne Univ, France
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- Darlay, R. (author)
- Newcastle Univ, England
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- Peltier, J. (author)
- Newcastle Univ, England
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- Palmer, J. M. (author)
- Newcastle Univ, England
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- Younes, R. (author)
- Newcastle Univ, England; Univ Turin, Italy
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- Tiniakos, D. (author)
- Newcastle Univ, England; Natl & Kapodistrian Univ Athens, Greece
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- Aithal, G. P. (author)
- Nottingham Univ Hosp NHS Trust, England; Univ Nottingham, England
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- Allison, M. (author)
- Cambridge Univ NHS Fdn Trust, England
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- Vacca, M. (author)
- Univ Cambridge, England
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- Göransson, M. (author)
- AstraZeneca, Sweden
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- Berlinguer-Palmini, R. (author)
- Newcastle Univ, England
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- Clark, J. E. (author)
- Newcastle Univ, England
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- Drinnan, M. J. (author)
- Newcastle Univ, England
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- Yki-Järvinen, H. (author)
- Univ Helsinki, Finland; Univ Helsinki, Finland
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- Dufour, J. F. (author)
- Univ Bern, Switzerland; Univ Bern, Switzerland
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- Ekstedt, Mattias (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Mag- tarmmedicinska kliniken
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- Francque, S. (author)
- Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium
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- Petta, S. (author)
- Univ Palermo, Italy
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- Bugianesi, E. (author)
- Univ Turin, Italy
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- Schattenberg, J. M. (author)
- Univ Hosp Mainz, Germany
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- Day, C. P. (author)
- Newcastle Univ, England
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- Cordell, H. J. (author)
- Newcastle Univ, England
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- Topal, B. (author)
- Univ Hosp Leuven, Belgium; Katholieke Univ Leuven, Belgium
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- Clément, K. (author)
- Sorbonne Univ, France
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- Romeo, Stefano, 1976 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine,Univ Gothenburg, Sweden
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- Ratziu, V. (author)
- Univ Paris Diderot, France
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- Roskams, T. (author)
- Katholieke Univ Leuven, Belgium; Univ Hosp Leuven, Belgium
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- Daly, A. K. (author)
- Newcastle Univ, England
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- Anstee, Q. M. (author)
- Newcastle Univ, England; Newcastle Upon Tyne Hosp NHS Trust, England
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- Trost, M. (author)
- Newcastle Univ, England
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- Härtlova, A. (author)
- Univ Gothenburg, Sweden; Newcastle Univ, England
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(creator_code:org_t)
- Elsevier BV, 2022
- 2022
- English.
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In: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012
- Related links:
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http://www.journal-o...
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https://liu.diva-por... (primary) (Raw object)
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Gastroenterologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)
Keyword
- immunometabolism
- inflammation
- macrophages
- NASH
- macrophages; immunometabolism; NASH; inflammation
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Govaere, O.
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Petersen, S. K.
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Martinez-Lopez, ...
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Wouters, J.
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Van Haele, M.
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Mancina, Roselli ...
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show more...
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Oveis, Jamialahm ...
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Bilkei-Gorzo, O.
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Lassen, P. B.
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Darlay, R.
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Peltier, J.
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Palmer, J. M.
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Younes, R.
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Tiniakos, D.
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Aithal, G. P.
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Allison, M.
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Vacca, M.
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Göransson, M.
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Berlinguer-Palmi ...
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Clark, J. E.
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Drinnan, M. J.
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Yki-Järvinen, H.
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Dufour, J. F.
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Ekstedt, Mattias
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Francque, S.
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Petta, S.
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Bugianesi, E.
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Schattenberg, J. ...
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Day, C. P.
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Cordell, H. J.
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Topal, B.
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Clément, K.
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Romeo, Stefano, ...
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Ratziu, V.
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Roskams, T.
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Daly, A. K.
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Anstee, Q. M.
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Trost, M.
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Härtlova, A.
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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 Infectious Medic ...
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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 Gastroenterology ...
- Articles in the publication
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Journal of Hepat ...
- By the university
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University of Gothenburg
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Linköping University