Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins.
Animals
Cell Line
Diet, High-Fat
/ adverse effects
Dietary Sugars
/ adverse effects
Fatty Acids
/ metabolism
Fructose
/ adverse effects
Glucose
/ adverse effects
Lipogenesis
Liver
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mitochondria
/ drug effects
Mitochondrial Proteins
/ genetics
Obesity
/ metabolism
Protein Processing, Post-Translational
Transcription, Genetic
acetylation
fatty acid oxidation
fatty liver disease
fructose
glucose
ketohexokinase
mass spectrometry
mitochondria
obesity
sugar
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
received:
09
02
2018
revised:
06
05
2019
accepted:
05
09
2019
entrez:
3
10
2019
pubmed:
3
10
2019
medline:
4
9
2020
Statut:
ppublish
Résumé
Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.
Identifiants
pubmed: 31577934
pii: S1550-4131(19)30504-2
doi: 10.1016/j.cmet.2019.09.003
pmc: PMC7816129
mid: NIHMS1656221
pii:
doi:
Substances chimiques
Dietary Sugars
0
Fatty Acids
0
Mitochondrial Proteins
0
Fructose
30237-26-4
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
735-753.e4Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK040561
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK085610
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK121967
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK033201
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK031036
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK031036
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
Références
Biochemistry. 2000 Feb 1;39(4):712-7
pubmed: 10651636
Biochem J. 1977 Mar 15;162(3):601-9
pubmed: 869906
Nat Protoc. 2011 Jun;6(6):859-69
pubmed: 21637204
J Nutr. 2008 Aug;138(8):1452-5
pubmed: 18641190
Eur J Clin Nutr. 2012 Feb;66(2):201-8
pubmed: 21952692
J Clin Invest. 2016 Nov 1;126(11):4372-4386
pubmed: 27669460
Mol Metab. 2016 Apr 22;5(7):538-551
pubmed: 27408778
Nat Biotechnol. 2014 Aug;32(8):834-41
pubmed: 24997786
Gene. 2005 Dec 19;363:15-23
pubmed: 16289629
Dig Dis Sci. 2016 May;61(5):1282-93
pubmed: 26856717
Exp Mol Med. 2016 Jul 15;48(7):e245
pubmed: 27416781
Nat Rev Mol Cell Biol. 2014 Aug;15(8):536-50
pubmed: 25053359
Biochim Biophys Acta. 2011 Jun;1807(6):726-34
pubmed: 21692241
Nature. 2010 Mar 4;464(7285):121-5
pubmed: 20203611
Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):674-8
pubmed: 7904757
J Hepatol. 2008 Jun;48(6):993-9
pubmed: 18395287
Food Funct. 2012 Feb;3(2):141-9
pubmed: 22159273
J Clin Invest. 1977 Jul;60(1):265-70
pubmed: 874089
Trends Endocrinol Metab. 2011 Feb;22(2):60-5
pubmed: 21067942
Diabetes. 2016 Aug;65(8):2187-200
pubmed: 27207510
Hepatology. 2007 Mar;45(3):778-88
pubmed: 17326204
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6
pubmed: 23576753
PLoS One. 2013 Jul 29;8(7):e66923
pubmed: 23922646
Cell Metab. 2015 Apr 7;21(4):637-46
pubmed: 25863253
Biochem J. 2011 Feb 1;433(3):505-14
pubmed: 21044047
N Engl J Med. 2012 Oct 11;367(15):1397-406
pubmed: 22998340
Gastroenterology. 2001 Apr;120(5):1183-92
pubmed: 11266382
Diabetes. 2005 Feb;54(2):462-71
pubmed: 15677504
J Biol Chem. 2011 Apr 15;286(15):12983-90
pubmed: 21317437
Biochim Biophys Acta. 1976 Mar 26;424(3):386-95
pubmed: 1259967
Hepatology. 2010 Sep;52(3):934-44
pubmed: 20607689
Mol Cell Proteomics. 2015 May;14(5):1400-10
pubmed: 25724911
Sci Rep. 2016 Dec 12;6:38836
pubmed: 27941836
Cell Metab. 2017 Aug 1;26(2):394-406.e6
pubmed: 28768177
Amino Acids. 2015 Mar;47(3):603-15
pubmed: 25534430
N Engl J Med. 2012 Oct 11;367(15):1407-16
pubmed: 22998339
Mol Cell Proteomics. 2012 Jun;11(6):O111.016717
pubmed: 22261725
J Biol Chem. 2013 Nov 22;288(47):33837-47
pubmed: 24121500
Aging Cell. 2009 Sep;8(5):604-6
pubmed: 19594485
J Biol Chem. 2014 Oct 31;289(44):30470-80
pubmed: 25204652
J Clin Invest. 2010 Dec;120(12):4316-31
pubmed: 21084751
JAMA. 1999 Nov 3;282(17):1659-64
pubmed: 10553793
Mol Cell Proteomics. 2013 Sep;12(9):2381-2
pubmed: 23756428
PLoS One. 2018 Dec 26;13(12):e0208973
pubmed: 30586434
BMC Obes. 2016 Dec 7;3:51
pubmed: 27980795
PLoS One. 2013 Sep 20;8(9):e75868
pubmed: 24073283
Acta Med Scand Suppl. 1972;542:205-14
pubmed: 4146849
Hepatology. 2010 Jun;51(6):1961-71
pubmed: 20301112
J Clin Invest. 2017 Nov 1;127(11):4059-4074
pubmed: 28972537
Biochem Soc Trans. 2002 Nov;30(Pt 6):1064-70
pubmed: 12440973
Mol Cell. 2006 Aug;23(4):607-18
pubmed: 16916647
Biol Chem. 2012 Jul;393(7):547-64
pubmed: 22944659
Nat Commun. 2014 Dec 09;5:5711
pubmed: 25487825
Antioxid Redox Signal. 2015 Apr 1;22(10):848-70
pubmed: 25602171
Nat Methods. 2017 Jun 29;14(7):646-647
pubmed: 28661500
Clin Interv Aging. 2016 Nov 30;11:1763-1771
pubmed: 27942207
Mol Cell. 2011 Oct 21;44(2):177-90
pubmed: 21856199
J Cell Physiol. 2007 Jan;210(1):1-6
pubmed: 17063460
Hepatology. 2008 Nov;48(5):1506-16
pubmed: 18924245
Pediatr Res. 1994 Oct;36(4):436-40
pubmed: 7816517
EMBO J. 2015 Nov 3;34(21):2620-32
pubmed: 26358839
J Hepatol. 2015 Aug;63(2):462-9
pubmed: 26055949
J Hepatol. 2002 Jul;37(1):56-62
pubmed: 12076862
Mol Cell Biol. 2007 Dec;27(24):8807-14
pubmed: 17923681