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Integrative study o...
Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target
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Smati, S. (author)
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Polizzi, A. (author)
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Fougerat, A. (author)
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show more...
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Ellero-Simatos, S. (author)
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Blum, Y. (author)
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Lippi, Y. (author)
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Régnier, M. (author)
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Laroyenne, A. (author)
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Huillet, M. (author)
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- Arif, Muhammad (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Zhang, Cheng (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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Lasserre, F. (author)
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Marrot, A. (author)
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Al Saati, T. (author)
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Wan, J. (author)
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Sommer, C. (author)
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Naylies, C. (author)
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Batut, A. (author)
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Lukowicz, C. (author)
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Fougeray, T. (author)
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Tramunt, B. (author)
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Dubot, P. (author)
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Smith, L. (author)
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Bertrand-Michel, J. (author)
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Hennuyer, N. (author)
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Pradere, J. -P (author)
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Staels, B. (author)
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Burcelin, R. (author)
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Lenfant, F. (author)
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Arnal, J. (author)
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Levade, T. (author)
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Gamet-Payrastre, L. (author)
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Lagarrigue, S. (author)
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Loiseau, N. (author)
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Lotersztajn, S. (author)
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Postic, C. (author)
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Wahli, W. (author)
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Bureau, C. (author)
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Guillaume, M. (author)
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- Mardinoglu, Adil (author)
- KTH,Science for Life Laboratory, SciLifeLab,Systembiologi
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Montagner, A. (author)
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Gourdy, P. (author)
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Guillou, H. (author)
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(creator_code:org_t)
- 2021-04-26
- 2022
- English.
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In: Gut. - : BMJ Publishing Group. - 0017-5749 .- 1468-3288. ; 71:4, s. 807-821
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- We evaluated the influence of sex on the pathophysiology of non-alcoholic fatty liver disease (NAFLD). We investigated diet-induced phenotypic responses to define sex-specific regulation between healthy liver and NAFLD to identify influential pathways in different preclinical murine models and their relevance in humans. Different models of diet-induced NAFLD (high-fat diet, choline-deficient high-fat diet, Western diet or Western diet supplemented with fructose and glucose in drinking water) were compared with a control diet in male and female mice. We performed metabolic phenotyping, including plasma biochemistry and liver histology, untargeted large-scale approaches (liver metabolome, lipidome and transcriptome), gene expression profiling and network analysis to identify sex-specific pathways in the mouse liver. The different diets induced sex-specific responses that illustrated an increased susceptibility to NAFLD in male mice. The most severe lipid accumulation and inflammation/fibrosis occurred in males receiving the high-fat diet and Western diet, respectively. Sex-biased hepatic gene signatures were identified for these different dietary challenges. The peroxisome proliferator-activated receptor α (PPARα) co-expression network was identified as sexually dimorphic, and in vivo experiments in mice demonstrated that hepatocyte PPARα determines a sex-specific response to fasting and treatment with pemafibrate, a selective PPARα agonist. Liver molecular signatures in humans also provided evidence of sexually dimorphic gene expression profiles and the sex-specific co-expression network for PPARα. These findings underscore the sex specificity of NAFLD pathophysiology in preclinical studies and identify PPARα as a pivotal, sexually dimorphic, pharmacological target. NCT02390232.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- gene expression
- lipid metabolism
- liver metabolism
- nonalcoholic steatohepatitis
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
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Gut
(Search for host publication in LIBRIS)
To the university's database
- By the author/editor
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Smati, S.
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Polizzi, A.
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Fougerat, A.
-
Ellero-Simatos, ...
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Blum, Y.
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Lippi, Y.
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show more...
-
Régnier, M.
-
Laroyenne, A.
-
Huillet, M.
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Arif, Muhammad
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Zhang, Cheng
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Lasserre, F.
-
Marrot, A.
-
Al Saati, T.
-
Wan, J.
-
Sommer, C.
-
Naylies, C.
-
Batut, A.
-
Lukowicz, C.
-
Fougeray, T.
-
Tramunt, B.
-
Dubot, P.
-
Smith, L.
-
Bertrand-Michel, ...
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Hennuyer, N.
-
Pradere, J. -P
-
Staels, B.
-
Burcelin, R.
-
Lenfant, F.
-
Arnal, J.
-
Levade, T.
-
Gamet-Payrastre, ...
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Lagarrigue, S.
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Loiseau, N.
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Lotersztajn, S.
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Postic, C.
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Wahli, W.
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Bureau, C.
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Guillaume, M.
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Mardinoglu, Adil
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Montagner, A.
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Gourdy, P.
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Guillou, H.
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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 Endocrinology an ...
- Articles in the publication
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Gut
- By the university
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Royal Institute of Technology