GSE157049
GSE GEORNA-seq of metformin treatment in liver in WT, Raptor Ser-Ala mutant, Tsc2-null, Raptor mutant;Tsc2-null, and Ampk-null
Relations
Summary
Despite being the frontline therapy for Type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill-defined. Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB. But several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1. Here we investigated the role of direct AMPK-mediated serine phosphorylation of RAPTOR in a new RaptorAA mouse model, in which AMPK phospho-serine sites Ser722 and Ser792 of RAPTOR were mutated to alanine. Metformin treatment of intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for the transcriptional response to metformin. Transcriptionally, AMPK and mTORC1 were both important for regulation of anabolic metabolism and inflammatory programs triggered by metformin treatment. The hepatic transcriptional response in mice on high fat diet treated with metformin was largely ablated by AMPK-deficiency under the conditions examined, indicating the essential role of this kinase and its targets in metformin action in vivo.
Overall Design
Mice maintained on 45% high fat diet for 12 weeks, fasted overnight, refed for 1h, and treated with 200 mpk metformin or saline for 4 hours
Analysis (14 steps)
View Data Processing- Raw RNA sequencing reads in FASTQ files were quality-tested using FASTQC (v0.11.8) (Andrews 2010) and mapped to the mouse reference genome (mm10) with STAR (v2.5.3a) aligner with default parameters (Dobin et al.
- 2012).
- Raw or normalized gene expression levels were quantified across all the exons of RefSeq genes with analyzeRepeats.pl in HOMER (v4.11.1) (Heinz et al.
- 2010).
- Differential expression analysis was performed with raw gene counts using R package, edgeR (v3.26.7) (Robinson et al.
- 2010), using replicates to compute within-group dispersion and correcting for batch effects.
- Genes with false discovery rate (FDR) < 0.05 and an absolute fold-change (FC) >= 1.5 were identified as significantly different when comparing two conditions.
- Normalized counts were log transformed, filtered, scaled, and centered prior to clustering and heatmap generation with Cluster3 (de Hoon et al.
Supplementary Files (1)
GEO Samples (29)
Dataset Citations (1)
SRA Experiments (29) and Runs (29)
Total: 26467 MBSample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539831 | 29721943 | 3031638186 | 835.91 | 1362_WTSal_JVN3_S3_R1_001.fastq.gz, 1362_WTSal_JVN3_S3_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539832 | 24666921 | 2516025942 | 697.52 | 4354_WTSal_JVN1_S1_R1_001.fastq.gz, 4354_WTSal_JVN1_S1_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539833 | 31127183 | 3174972666 | 877.55 | 4357_WTSal_JVN2_S2_R1_001.fastq.gz, 4357_WTSal_JVN2_S2_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539834 | 39000252 | 3978025704 | 1088.39 | 1087_WTMet_JVN6_S6_R1_001.fastq.gz, 1087_WTMet_JVN6_S6_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539835 | 35231934 | 3593657268 | 987.2 | 4359_WTMet_JVN4_S4_R1_001.fastq.gz, 4359_WTMet_JVN4_S4_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539836 | 34874431 | 3557191962 | 976.47 | 4360_WTMet_JVN5_S5_R1_001.fastq.gz, 4360_WTMet_JVN5_S5_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539837 | 33378187 | 3404575074 | 931.78 | 1268_AASal_JVN8_S8_R1_001.fastq.gz, 1268_AASal_JVN8_S8_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539838 | 35586259 | 3629798418 | 1004.64 | 1269_AASal_JVN9_S9_R1_001.fastq.gz, 1269_AASal_JVN9_S9_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539839 | 31988719 | 3262849338 | 894.77 | 1289_AASal_JVN7_S7_R1_001.fastq.gz, 1289_AASal_JVN7_S7_R2_001.fastq.g… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539840 | 34386731 | 3507446562 | 967.41 | 1202_AAMet_JVN12_S12_R1_001.fastq.gz, 1202_AAMet_JVN12_S12_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539841 | 36684477 | 3741816654 | 1036.6 | 1277_AAMet_JVN10_S10_R1_001.fastq.gz, 1277_AAMet_JVN10_S10_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539842 | 32801104 | 3345712608 | 926.2 | 1367_AAMet_JVN11_S11_R1_001.fastq.gz, 1367_AAMet_JVN11_S11_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539843 | 27474886 | 2802438372 | 790.15 | 1038_TSCSal_JVN13_S13_R1_001.fastq.gz, 1038_TSCSal_JVN13_S13_R2_001.f… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539844 | 30508247 | 3111841194 | 859.08 | 1364_TSCSal_JVN14_S14_R1_001.fastq.gz, 1364_TSCSal_JVN14_S14_R2_001.f… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539845 | 30425446 | 3103395492 | 857.89 | 1291_TSCMet_JVN17_S17_R1_001.fastq.gz, 1291_TSCMet_JVN17_S17_R2_001.f… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539846 | 31648110 | 3228107220 | 891.07 | 1369_TSCMet_JVN15_S15_R1_001.fastq.gz, 1369_TSCMet_JVN15_S15_R2_001.f… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539847 | 28453626 | 2902269852 | 800.46 | 1373_TSCMet_JVN16_S16_R1_001.fastq.gz, 1373_TSCMet_JVN16_S16_R2_001.f… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539848 | 29677881 | 3027143862 | 838.91 | 1039_ATSal_JVN18_S18_R1_001.fastq.gz, 1039_ATSal_JVN18_S18_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539849 | 30283556 | 3088922712 | 850.47 | 1406_ATSal_JVN20_S20_R1_001.fastq.gz, 1406_ATSal_JVN20_S20_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539850 | 25912553 | 2643080406 | 728.54 | 1069_ATSal_JVN19_S19_R1_001.fastq.gz, 1069_ATSal_JVN19_S19_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539851 | 37574621 | 3832611342 | 1065.05 | 1408_ATMet_JVN22_S22_R1_001.fastq.gz, 1408_ATMet_JVN22_S22_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539852 | 34696654 | 3539058708 | 979.66 | 1071_ATMet_JVN23_S23_R1_001.fastq.gz, 1071_ATMet_JVN23_S23_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539853 | 36040637 | 3676144974 | 1029.37 | 1407_ATMet_JVN21_S21_R1_001.fastq.gz, 1407_ATMet_JVN21_S21_R2_001.fas… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539854 | 34033338 | 3471400476 | 958.49 | 4355_AdelSal_JVN24_S24_R1_001.fastq.gz, 4355_AdelSal_JVN24_S24_R2_001… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539855 | 37566733 | 3831806766 | 1058.61 | 4356_AdelSal_JVN25_S25_R1_001.fastq.gz, 4356_AdelSal_JVN25_S25_R2_001… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539856 | 35481959 | 3619159818 | 997.86 | 4363_AdelSal_JVN26_S26_R1_001.fastq.gz, 4363_AdelSal_JVN26_S26_R2_001… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539857 | 32292134 | 3293797668 | 908.13 | 4364_AdelMet_JVN27_S27_R1_001.fastq.gz, 4364_AdelMet_JVN27_S27_R2_001… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539858 | 29072018 | 2965345836 | 819.01 | 4365_AdelMet_JVN28_S28_R1_001.fastq.gz, 4365_AdelMet_JVN28_S28_R2_001… | SRA |
Sample attributes
Original files (1)
Runs (1)
| Run | Spots | Bases | Size (MB) | Files | Link |
|---|---|---|---|---|---|
| SRR12539859 | 28853220 | 2943028440 | 809.51 | 4330_AdelMet_JVN29_S29_R1_001.fastq.gz, 4330_AdelMet_JVN29_S29_R2_001… | SRA |
Linked Publications (1)
Data Files (29)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | 1038_TSCSal_JVN13_S13_R1_001.fastq.gz | RNA-Seq | 790.1 MB | link | |||
| — | 1039_ATSal_JVN18_S18_R1_001.fastq.gz | RNA-Seq | 838.9 MB | link | |||
| — | 1069_ATSal_JVN19_S19_R1_001.fastq.gz | RNA-Seq | 728.5 MB | link | |||
| — | 1071_ATMet_JVN23_S23_R1_001.fastq.gz | RNA-Seq | 979.7 MB | link | |||
| — | 1087_WTMet_JVN6_S6_R1_001.fastq.gz | RNA-Seq | 1.1 GB | link | |||
| — | 1202_AAMet_JVN12_S12_R1_001.fastq.gz | RNA-Seq | 967.4 MB | link | |||
| — | 1268_AASal_JVN8_S8_R1_001.fastq.gz | RNA-Seq | 931.8 MB | link | |||
| — | 1269_AASal_JVN9_S9_R1_001.fastq.gz | RNA-Seq | 1004.6 MB | link | |||
| — | 1277_AAMet_JVN10_S10_R1_001.fastq.gz | RNA-Seq | 1.0 GB | link | |||
| — | 1289_AASal_JVN7_S7_R1_001.fastq.gz | RNA-Seq | 894.8 MB | link | |||
| — | 1291_TSCMet_JVN17_S17_R1_001.fastq.gz | RNA-Seq | 857.9 MB | link | |||
| — | 1362_WTSal_JVN3_S3_R1_001.fastq.gz | RNA-Seq | 835.9 MB | link | |||
| — | 1364_TSCSal_JVN14_S14_R1_001.fastq.gz | RNA-Seq | 859.1 MB | link | |||
| — | 1367_AAMet_JVN11_S11_R1_001.fastq.gz | RNA-Seq | 926.2 MB | link | |||
| — | 1369_TSCMet_JVN15_S15_R1_001.fastq.gz | RNA-Seq | 891.1 MB | link | |||
| — | 1373_TSCMet_JVN16_S16_R1_001.fastq.gz | RNA-Seq | 800.5 MB | link | |||
| — | 1406_ATSal_JVN20_S20_R1_001.fastq.gz | RNA-Seq | 850.5 MB | link | |||
| — | 1407_ATMet_JVN21_S21_R1_001.fastq.gz | RNA-Seq | 1.0 GB | link | |||
| — | 1408_ATMet_JVN22_S22_R1_001.fastq.gz | RNA-Seq | 1.0 GB | link | |||
| — | 4330_AdelMet_JVN29_S29_R1_001.fastq.gz | RNA-Seq | 809.5 MB | link | |||
| — | 4354_WTSal_JVN1_S1_R1_001.fastq.gz | RNA-Seq | 697.5 MB | link | |||
| — | 4355_AdelSal_JVN24_S24_R1_001.fastq.gz | RNA-Seq | 958.5 MB | link | |||
| — | 4356_AdelSal_JVN25_S25_R1_001.fastq.gz | RNA-Seq | 1.0 GB | link | |||
| — | 4357_WTSal_JVN2_S2_R1_001.fastq.gz | RNA-Seq | 877.5 MB | link | |||
| — | 4359_WTMet_JVN4_S4_R1_001.fastq.gz | RNA-Seq | 987.2 MB | link | |||
| — | 4360_WTMet_JVN5_S5_R1_001.fastq.gz | RNA-Seq | 976.5 MB | link | |||
| — | 4363_AdelSal_JVN26_S26_R1_001.fastq.gz | RNA-Seq | 997.9 MB | link | |||
| — | 4364_AdelMet_JVN27_S27_R1_001.fastq.gz | RNA-Seq | 908.1 MB | link | |||
| — | 4365_AdelMet_JVN28_S28_R1_001.fastq.gz | RNA-Seq | 819.0 MB | link |