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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: RNA profiles of metabolically active tissues.

ABSTRACT: A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: RNA profiles of metabolically active tissues.

PROVIDER: PRJNA497100 | ENA |

REPOSITORIES: ENA

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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: RNA profiles of metabolically active tissues.

Project description:Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcrips with elusive functions in metabolism. Here we report that an unexpectedly high fraction of lncRNAs, but not protein-coding mRNAs, is repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation specifically induced lncRNAs in mouse liver. Similarly, lncRNAs were lost in diabetic humans. LncRNA promoter analyses, global cistrome and gain-of-function analyses confirmed that increased MAFG signaling during DIO curbs lncRNA expression. Silencing Mafg in primary hepatocytes and in vivo elicited a fasting-like expression profile, improved glucose metabolism, derepressed lncRNAs and prevented mammalian target of rapamycin (mTOR)-driven protein translation. We found that obesity-repressed lincIRS2 is controlled by MAFG and observed that genetic and RNAi-mediated lincIRS2 loss causes hyperglycemia, insulin resistance and aberrant glucose output in lean mice. Taken together, we identify a novel MAFG-lncRNA axis controlling hepatic glucose metabolism in health and metabolic disease.

2019-12-18 | GSE121345 | GEO

A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism.

Project description:A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism.

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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: Liver RNA seq profiles of mice fed different feeding regimes.

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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism.

Project description:This SuperSeries is composed of the SubSeries listed below.

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A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: Liver RNA profiles of lean non-diabetic, obese non-diabetic as well as obese diabetic humans.

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