MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic stea...

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Autores principales:	Ashley M Miller, Derek S Gilchrist, Jagtar Nijjar, Elisa Araldi, Cristina M Ramirez, Christopher A Lavery, Carlos Fernández-Hernando, Iain B McInnes, Mariola Kurowska-Stolarska
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8508583358914a5dae77f177289ea05d
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spelling	oai:doaj.org-article:8508583358914a5dae77f177289ea05d2021-11-18T08:58:33ZMiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.1932-620310.1371/journal.pone.0072324https://doaj.org/article/8508583358914a5dae77f177289ea05d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23991091/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155(-/-) mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155(-/-) livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155(-/-) mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes.Ashley M MillerDerek S GilchristJagtar NijjarElisa AraldiCristina M RamirezChristopher A LaveryCarlos Fernández-HernandoIain B McInnesMariola Kurowska-StolarskaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72324 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ashley M Miller Derek S Gilchrist Jagtar Nijjar Elisa Araldi Cristina M Ramirez Christopher A Lavery Carlos Fernández-Hernando Iain B McInnes Mariola Kurowska-Stolarska MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
description	Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155(-/-) mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155(-/-) livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155(-/-) mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes.
format	article
author	Ashley M Miller Derek S Gilchrist Jagtar Nijjar Elisa Araldi Cristina M Ramirez Christopher A Lavery Carlos Fernández-Hernando Iain B McInnes Mariola Kurowska-Stolarska
author_facet	Ashley M Miller Derek S Gilchrist Jagtar Nijjar Elisa Araldi Cristina M Ramirez Christopher A Lavery Carlos Fernández-Hernando Iain B McInnes Mariola Kurowska-Stolarska
author_sort	Ashley M Miller
title	MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
title_short	MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
title_full	MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
title_fullStr	MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
title_full_unstemmed	MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
title_sort	mir-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8508583358914a5dae77f177289ea05d
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MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.

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