Multiomics reveals multilevel control of renal and systemic metabolism by the renal tubular circadian clock.
Bioenergetics
Bioinformatics
Fatty acid oxidation
Nephrology
Journal
The Journal of clinical investigation
ISSN: 1558-8238
Titre abrégé: J Clin Invest
Pays: United States
ID NLM: 7802877
Informations de publication
Date de publication:
17 04 2023
17 04 2023
Historique:
received:
14
11
2022
accepted:
23
02
2023
medline:
18
4
2023
pubmed:
3
3
2023
entrez:
2
3
2023
Statut:
epublish
Résumé
Circadian rhythmicity in renal function suggests rhythmic adaptations in renal metabolism. To decipher the role of the circadian clock in renal metabolism, we studied diurnal changes in renal metabolic pathways using integrated transcriptomic, proteomic, and metabolomic analysis performed on control mice and mice with an inducible deletion of the circadian clock regulator Bmal1 in the renal tubule (cKOt). With this unique resource, we demonstrated that approximately 30% of RNAs, approximately 20% of proteins, and approximately 20% of metabolites are rhythmic in the kidneys of control mice. Several key metabolic pathways, including NAD+ biosynthesis, fatty acid transport, carnitine shuttle, and β-oxidation, displayed impairments in kidneys of cKOt mice, resulting in perturbed mitochondrial activity. Carnitine reabsorption from primary urine was one of the most affected processes with an approximately 50% reduction in plasma carnitine levels and a parallel systemic decrease in tissue carnitine content. This suggests that the circadian clock in the renal tubule controls both kidney and systemic physiology.
Identifiants
pubmed: 36862511
pii: 167133
doi: 10.1172/JCI167133
pmc: PMC10104904
doi:
pii:
Substances chimiques
Carnitine
S7UI8SM58A
ARNTL Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Genome Res. 2021 Jan 12;:
pubmed: 33436377
J Am Soc Nephrol. 2014 Jul;25(7):1430-9
pubmed: 24652800
SLAS Discov. 2019 Feb;24(2):89-110
pubmed: 30523710
Cell Metab. 2015 Oct 6;22(4):709-20
pubmed: 26365180
PLoS Genet. 2014 Jan;10(1):e1004047
pubmed: 24391516
Front Physiol. 2021 Sep 17;12:723690
pubmed: 34603081
J Biol Chem. 2014 Apr 25;289(17):11791-11806
pubmed: 24610784
Protein Cell. 2020 Sep;11(9):661-679
pubmed: 32277346
Nat Rev Nephrol. 2020 Feb;16(2):99-111
pubmed: 31673160
Biochem Biophys Res Commun. 1998 May 29;246(3):589-95
pubmed: 9618255
Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16523-8
pubmed: 19805330
Clin Cancer Res. 2010 Oct 1;16(19):4789-99
pubmed: 20858838
Nature. 2010 Mar 4;464(7285):121-5
pubmed: 20203611
Nat Rev Neurosci. 2018 Aug;19(8):453-469
pubmed: 29934559
Int Neurourol J. 2019 Dec;23(4):258-264
pubmed: 31905272
Am J Physiol Renal Physiol. 2020 Jun 1;318(6):F1463-F1477
pubmed: 32338037
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):167-72
pubmed: 24344304
Proc Natl Acad Sci U S A. 2021 Jan 19;118(3):
pubmed: 33452134
Cell Metab. 2015 Apr 7;21(4):637-46
pubmed: 25863253
Cell Metab. 2015 Jul 7;22(1):31-53
pubmed: 26118927
PLoS One. 2014 Nov 12;9(11):e112811
pubmed: 25389966
Nature. 2018 Nov;563(7731):354-359
pubmed: 30356218
Am J Physiol Renal Physiol. 2015 Dec 1;309(11):F933-42
pubmed: 26377793
J Biol Rhythms. 2017 Oct;32(5):380-393
pubmed: 29098954
Nat Rev Nephrol. 2018 Oct;14(10):626-635
pubmed: 30143787
PLoS One. 2011;6(8):e23295
pubmed: 21858060
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Science. 2013 Nov 1;342(6158):1243417
pubmed: 24051248
Bioinformatics. 2012 Jan 1;28(1):112-8
pubmed: 22039212
Nat Commun. 2018 Apr 19;9(1):1553
pubmed: 29674717
Sci Rep. 2019 Nov 6;9(1):16089
pubmed: 31695128
J Clin Invest. 1950 Feb;29(2):187-92
pubmed: 15403982
Kidney Int. 2001 May;59(5):1873-80
pubmed: 11318959
Cell Metab. 2017 Jan 10;25(1):102-117
pubmed: 27818260
J Clin Invest. 2022 Feb 1;132(3):
pubmed: 35104800
Kidney Int. 2022 Mar;101(3):563-573
pubmed: 34838539
J Occup Environ Med. 2013 Nov;55(11):1323-8
pubmed: 24164760
Clin Chim Acta. 1989 Jul 31;183(1):3-11
pubmed: 2670337
Molecules. 2019 Sep 06;24(18):
pubmed: 31500110
Kidney Int. 2020 Apr;97(4):728-740
pubmed: 31948598
J Am Soc Nephrol. 2016 Oct;27(10):2997-3004
pubmed: 27056296
Science. 2009 May 1;324(5927):651-4
pubmed: 19299583
Nat Commun. 2021 Jun 17;12(1):3683
pubmed: 34140503
Nat Commun. 2016 Oct 11;7:13103
pubmed: 27725675
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Science. 2019 Oct 11;366(6462):
pubmed: 31601739
Handb Exp Pharmacol. 2013;(217):45-66
pubmed: 23604475
Nat Med. 2008 Sep;14(9):979-84
pubmed: 18724376
Nat Commun. 2021 Aug 17;12(1):4992
pubmed: 34404777
Front Physiol. 2017 Apr 06;8:205
pubmed: 28428757
Science. 2009 May 1;324(5927):654-7
pubmed: 19286518
J Lab Clin Med. 1992 Sep;120(3):400-10
pubmed: 1517687
J Am Soc Nephrol. 2012 Jun;23(6):1019-26
pubmed: 22440902
Genome Med. 2019 Dec 17;11(1):82
pubmed: 31847894
Genome Res. 2018 Feb;28(2):182-191
pubmed: 29254942
Mol Genet Metab. 2001 Aug;73(4):287-97
pubmed: 11509010
Kidney Int. 2005 Apr;67(4):1410-9
pubmed: 15780093
J Clin Invest. 1952 Mar;31(3):326-34
pubmed: 14917748
PLoS Genet. 2014 Oct 16;10(10):e1004695
pubmed: 25330117
Biostatistics. 2012 Jul;13(3):539-52
pubmed: 22101192
Biochemistry. 2010 Jan 19;49(2):304-11
pubmed: 20000467
Clin J Am Soc Nephrol. 2011 Jun;6(6):1258-65
pubmed: 21415310
Nat Med. 2013 Aug;19(8):1039-46
pubmed: 23852339
Cell Death Dis. 2020 Nov 20;11(11):994
pubmed: 33219209
Nat Methods. 2016 Sep;13(9):731-40
pubmed: 27348712
Cell Metab. 2018 Mar 6;27(3):657-666.e5
pubmed: 29478834
Cell Rep. 2017 Aug 15;20(7):1729-1743
pubmed: 28813682
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Chronobiol Int. 1996 Nov;13(5):349-58
pubmed: 8957586
Toxins (Basel). 2020 Feb 28;12(3):
pubmed: 32121234