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| Status |
Public on Dec 18, 2019 |
| Title |
A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism: Liver RNA profiles of mice injected with control, Mafg and LncIRS2 LNA. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Liver RNA profiles of 18-week-old mice injected with control, Mafg and LncIRS2 LNA respectively, were generated by deep sequencing, in four replicates on Illumina HiSeq 4000.
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| Contributor(s) |
Pradas-Juni M, Hansmeier NR, Link JC, Schmidt E, Klemm P, Fernandez-Rebollo E, Loureiro R, Dhouadi I, Kiefer CA, Larsen BD, Schwarzer R, Khani S, Oliverio M, Topel H, Awazawa M, Frommolt P, Heeren J, Scheja L, Dieterich C, Büning H, Yang L, Cao H, De Jesus DF, Kulkarni RN, Zevnik B, Tröder SE, Knippschild U, Edwards PA, Lee RG, Yamamoto M, de Aguiar Vallim TQ, Kornfeld J |
| Citation(s) |
32005828 |
| Submission date |
Oct 16, 2018 |
| Last update date |
Feb 10, 2020 |
| Contact name |
Jan Wilhelm Kornfeld |
| E-mail(s) |
janwilhelmkornfeld@bmb.sdu.dk
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| Organization name |
University of Southern Denmark
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| Department |
Biochemistry and Molecular Biology
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| Lab |
Noncoding Kornfeld Lab - Principles of Energy Homeostasis
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| Street address |
Campusbej 50
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| City |
Odense |
| ZIP/Postal code |
5230 |
| Country |
Denmark |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (24)
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| This SubSeries is part of SuperSeries: |
| GSE121346 |
A MAFG-lncRNA axis links systemic nutrient abundance to hepatic glucose metabolism. |
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| Relations |
| BioProject |
PRJNA497097 |
| SRA |
SRP165897 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121343_SupplementaryData7_RNA-Seq_MAFG_LNA_HFD--SCR_LNA_HFD_.xlsx |
17.9 Mb |
(ftp)(http) |
XLSX |
| GSE121343_SupplementaryData8_RNA-Seq_SCR_LNA_CD--SCR_LNA_HFD_.xlsx |
17.8 Mb |
(ftp)(http) |
XLSX |
| GSE121343_SupplementaryData9_RNA-Seq_SCR_LNA_CD--LNCIRS2_LNA_CD_.xlsx |
17.8 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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