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| Status |
Public on May 16, 2024 |
| Title |
Hydroxycitrate promotes muscle regeneration and delays early mortality in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
ATP-citrate lyase (ACLY) inhibitors have the potential of modulating central processes in protein, carbohydrate, and lipid metabolism, which can have relevant physiological consequences in aging and age-related diseases. Here, we show that hepatic phospho-active ACLY correlates with overweight and Model for End-stage Liver Disease score in humans. Wild-type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB-204990 and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy-fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced a profound modulation of regenerative processes. In vivo, potassium hydroxycitrate modulated physical performance towards increases in maximal force and reduced endurance in healthy-fed mice, and produced improvements in locomotor function in mice exposed to cardiotoxin-induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in relevant aspects of aging and muscle regeneration.
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| Overall design |
C57BL/6 male mice were divided in different groups with a standard diet or standard diet supplemented with hydroxycitrate. AML12 cells were siRNA interfered for Acly expression and were treated with hydroxycitrate, SB-204990 or Bempedoic acid. RNAseq was performed from AML12 cells, liver, soleo and gastrocnemius.
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| Contributor(s) |
Espadas I, Cáliz-Molina M, López-Fernández-Sobrino R, Panadero-Morón C, Sola-García A, Soriano-Navarro M, Martínez-Force E, Venegas-Calderón M, Salas JJ, Martín F, Gauthier BR, Alfaro-Cerbelló C, Martí-Aguado D, Capilla-González V, Martín-Montalvo A |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 18, 2023 |
| Last update date |
May 16, 2024 |
| Contact name |
Alejandro Martin-Montalvo |
| E-mail(s) |
alejandro.martinmontalvo@cabimer.es
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| Organization name |
CABIMER
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| Street address |
Av/ Américo Vespucio 24
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| City |
Seville |
| ZIP/Postal code |
41092 |
| Country |
Spain |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (59)
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| GSM7384367 |
Liver_STD, rep4 |
| GSM7384368 |
Liver_STD, rep5 |
| GSM7384369 |
Liver_HCA, rep1 |
| GSM7384370 |
Liver_HCA, rep2 |
| GSM7384371 |
Liver_HCA, rep3 |
| GSM7384372 |
Liver_HCA, rep4 |
| GSM7384373 |
Liver_HCA, rep5 |
| GSM7384374 |
Soleo_STD, rep1 |
| GSM7384375 |
Soleo_STD, rep2 |
| GSM7384376 |
Soleo_STD, rep3 |
| GSM7384377 |
Soleo_STD, rep4 |
| GSM7384378 |
Soleo_STD, rep5 |
| GSM7384379 |
Soleo_HCA, rep1 |
| GSM7384380 |
Soleo_HCA, rep2 |
| GSM7384381 |
Soleo_HCA, rep3 |
| GSM7384382 |
Soleo_HCA, rep4 |
| GSM7384383 |
Soleo_HCA, rep5 |
| GSM7974044 |
Gastrocnemius, GEN202_23_54 |
| GSM7974045 |
Gastrocnemius, GEN202_23_107 |
| GSM7974046 |
Gastrocnemius, GEN202_23_53 |
| GSM7974047 |
Gastrocnemius, GEN202_23_55 |
| GSM7974048 |
Gastrocnemius, GEN202_23_56 |
| GSM7974049 |
Gastrocnemius, GEN202_23_57 |
| GSM7974050 |
Gastrocnemius, GEN202_23_58 |
| GSM7974051 |
Gastrocnemius, GEN202_23_59 |
| GSM7974052 |
Gastrocnemius, GEN202_23_60 |
| GSM7974053 |
Gastrocnemius, GEN202_23_51 |
| GSM7974054 |
Gastrocnemius, GEN202_23_104 |
| GSM7974055 |
Gastrocnemius, GEN202_23_50 |
| GSM7974056 |
Gastrocnemius, GEN202_23_63 |
| GSM7974057 |
Gastrocnemius, GEN202_23_61 |
| GSM7974058 |
Gastrocnemius, GEN202_23_62 |
| GSM7974059 |
AML12 cells, GEN202_23_1 |
| GSM7974060 |
AML12 cells, GEN202_23_2 |
| GSM7974061 |
AML12 cells, GEN202_23_13 |
| GSM7974062 |
AML12 cells, GEN202_23_7 |
| GSM7974063 |
AML12 cells, GEN202_23_8 |
| GSM7974064 |
AML12 cells, GEN202_23_82 |
| GSM7974065 |
AML12 cells, GEN202_23_4 |
| GSM7974066 |
AML12 cells, GEN202_23_5 |
| GSM7974067 |
AML12 cells, GEN202_23_81 |
| GSM7974068 |
AML12 cells, GEN202_23_11 |
| GSM7974069 |
AML12 cells, GEN202_23_10 |
| GSM7974070 |
AML12 cells, GEN202_23_83 |
| GSM7974071 |
AML12 cells, GEN202_23_84 |
| GSM7974072 |
AML12 cells, GEN202_23_14 |
| GSM7974073 |
AML12 cells, GEN202_23_15 |
| GSM7974074 |
AML12 cells, GEN202_23_19 |
| GSM7974075 |
AML12 cells, GEN202_23_20 |
| GSM7974076 |
AML12 cells, GEN202_23_86 |
| GSM7974077 |
AML12 cells, GEN202_23_17 |
| GSM7974078 |
AML12 cells, GEN202_23_16 |
| GSM7974079 |
AML12 cells, GEN202_23_85 |
| GSM7974080 |
AML12 cells, GEN202_23_22 |
| GSM7974081 |
AML12 cells, GEN202_23_23 |
| GSM7974082 |
AML12 cells, GEN202_23_87 |
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| Relations |
| BioProject |
PRJNA974048 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232837_DEseq_Liver_STDvHCA.xlsx |
2.4 Mb |
(ftp)(http) |
XLSX |
| GSE232837_DEseq_Soleo_STDvHCA.xlsx |
2.5 Mb |
(ftp)(http) |
XLSX |
| GSE232837_STD_vs_LiverSTDvsHCA.genes.deseq.counts.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
| GSE232837_SoleoSTD_vs_SoleoSTDHCA.genes.deseq.counts.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
| GSE232837_control_vs_comparison.genes.deseq.countsAML12.csv.gz |
2.8 Mb |
(ftp)(http) |
CSV |
| GSE232837_control_vs_comparison.genes.deseq.countsCTX.csv.gz |
2.0 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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