RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output

Abstract Liver plays a key role in maintaining glucose homeostasis and impaired hepatic glucose metabolism is associated with type 2 diabetes. In the present study, we used RNA sequencing to profile the transcriptome of the livers of diabetic db/db mice as compared to the normal db/+ mice and identi...

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Autores principales:	Neha Goyal, Ambily Sivadas, K. V. Shamsudheen, Rijith Jayarajan, Ankit Verma, Sridhar Sivasubbu, Vinod Scaria, Malabika Datta
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e368d4dd85474897b1a7477fd6fe2d52
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spelling	oai:doaj.org-article:e368d4dd85474897b1a7477fd6fe2d522021-12-02T15:06:15ZRNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output10.1038/s41598-017-08281-72045-2322https://doaj.org/article/e368d4dd85474897b1a7477fd6fe2d522017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08281-7https://doaj.org/toc/2045-2322Abstract Liver plays a key role in maintaining glucose homeostasis and impaired hepatic glucose metabolism is associated with type 2 diabetes. In the present study, we used RNA sequencing to profile the transcriptome of the livers of diabetic db/db mice as compared to the normal db/+ mice and identified 218 differentially expressed genes. Amongst these, there were 3 lncRNAs that were significantly downregulated and H19 was the most altered lncRNA in the livers of db/db mice. H19 expression significantly correlated with the expression of genes of the glycolysis and gluconeogenesis pathways, which suggest that altered hepatic H19 levels can directly or indirectly modulate their expression. Inhibition of H19 using specific siRNA in HepG2 cells and primary mouse hepatocytes significantly increased the levels of gluconeogenic genes. This was subsequently accompanied by increased hepatic glucose output. Further,H19 depletion in HepG2 cells impaired insulin signaling and increased nuclear localization of FoxO1, an important transcriptional regulator of gluconeogenic gene expression. Our results reveal a novel link between decreased H19 levels and impaired gluconeogenesis via regulation of FoxO1 nuclear levels. These put forth interesting observations on the regulatory role of H19 in altering hepatic physiology during diabetes.Neha GoyalAmbily SivadasK. V. ShamsudheenRijith JayarajanAnkit VermaSridhar SivasubbuVinod ScariaMalabika DattaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neha Goyal Ambily Sivadas K. V. Shamsudheen Rijith Jayarajan Ankit Verma Sridhar Sivasubbu Vinod Scaria Malabika Datta RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
description	Abstract Liver plays a key role in maintaining glucose homeostasis and impaired hepatic glucose metabolism is associated with type 2 diabetes. In the present study, we used RNA sequencing to profile the transcriptome of the livers of diabetic db/db mice as compared to the normal db/+ mice and identified 218 differentially expressed genes. Amongst these, there were 3 lncRNAs that were significantly downregulated and H19 was the most altered lncRNA in the livers of db/db mice. H19 expression significantly correlated with the expression of genes of the glycolysis and gluconeogenesis pathways, which suggest that altered hepatic H19 levels can directly or indirectly modulate their expression. Inhibition of H19 using specific siRNA in HepG2 cells and primary mouse hepatocytes significantly increased the levels of gluconeogenic genes. This was subsequently accompanied by increased hepatic glucose output. Further,H19 depletion in HepG2 cells impaired insulin signaling and increased nuclear localization of FoxO1, an important transcriptional regulator of gluconeogenic gene expression. Our results reveal a novel link between decreased H19 levels and impaired gluconeogenesis via regulation of FoxO1 nuclear levels. These put forth interesting observations on the regulatory role of H19 in altering hepatic physiology during diabetes.
format	article
author	Neha Goyal Ambily Sivadas K. V. Shamsudheen Rijith Jayarajan Ankit Verma Sridhar Sivasubbu Vinod Scaria Malabika Datta
author_facet	Neha Goyal Ambily Sivadas K. V. Shamsudheen Rijith Jayarajan Ankit Verma Sridhar Sivasubbu Vinod Scaria Malabika Datta
author_sort	Neha Goyal
title	RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
title_short	RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
title_full	RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
title_fullStr	RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
title_full_unstemmed	RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output
title_sort	rna sequencing of db/db mice liver identifies lncrna h19 as a key regulator of gluconeogenesis and hepatic glucose output
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e368d4dd85474897b1a7477fd6fe2d52
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RNA sequencing of db/db mice liver identifies lncRNA H19 as a key regulator of gluconeogenesis and hepatic glucose output

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