Mitochondrial oxidative function in NAFLD: Friend or foe?
Animals
Blood Glucose
/ drug effects
Clinical Trials as Topic
Disease Models, Animal
Gluconeogenesis
/ drug effects
Humans
Hydrogen Peroxide
/ metabolism
Hyperglycemia
/ blood
Hypoglycemic Agents
/ pharmacology
Insulin
/ metabolism
Lipogenesis
/ drug effects
Liver
/ cytology
Mitochondria
/ drug effects
Non-alcoholic Fatty Liver Disease
/ blood
Oxidation-Reduction
/ drug effects
Oxidative Stress
/ drug effects
Signal Transduction
/ drug effects
Treatment Outcome
H(2)O(2)
Lipid metabolism
Mitochondria
Mitochondrial heterogeneity
Mitophagy
NAFLD
NASH
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
02
09
2020
revised:
17
11
2020
accepted:
26
11
2020
pubmed:
5
12
2020
medline:
8
3
2022
entrez:
4
12
2020
Statut:
ppublish
Résumé
Mitochondrial oxidative function plays a key role in the development of non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR). Recent studies reported that fatty liver might not be a result of decreased mitochondrial fat oxidation caused by mitochondrial damage. Rather, NAFLD and IR induce an elevation in mitochondrial function that covers the increased demand for carbon intermediates and ATP caused by elevated lipogenesis and gluconeogenesis. Furthermore, mitochondria play a role in regulating hepatic insulin sensitivity and lipogenesis by modulating redox-sensitive signaling pathways. We review the contradictory studies indicating that NAFLD and hyperglycemia can either increase or decrease mitochondrial oxidative capacity in the liver. We summarize mechanisms regulating mitochondrial heterogeneity inside the same cell and discuss how these mechanisms may determine the role of mitochondria in NAFLD. We further discuss the role of endogenous antioxidants in controlling mitochondrial H The balance of fat oxidation versus accumulation depends on mitochondrial fuel preference rather than ATP-synthesizing respiration. As such, therapies targeting fuel preference might be more suitable for treating NAFLD. Similarly, suppressing maladaptive antioxidants, rather than interfering with physiological mitochondrial H
Sections du résumé
BACKGROUND
Mitochondrial oxidative function plays a key role in the development of non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR). Recent studies reported that fatty liver might not be a result of decreased mitochondrial fat oxidation caused by mitochondrial damage. Rather, NAFLD and IR induce an elevation in mitochondrial function that covers the increased demand for carbon intermediates and ATP caused by elevated lipogenesis and gluconeogenesis. Furthermore, mitochondria play a role in regulating hepatic insulin sensitivity and lipogenesis by modulating redox-sensitive signaling pathways.
SCOPE OF REVIEW
We review the contradictory studies indicating that NAFLD and hyperglycemia can either increase or decrease mitochondrial oxidative capacity in the liver. We summarize mechanisms regulating mitochondrial heterogeneity inside the same cell and discuss how these mechanisms may determine the role of mitochondria in NAFLD. We further discuss the role of endogenous antioxidants in controlling mitochondrial H
MAJOR CONCLUSIONS
The balance of fat oxidation versus accumulation depends on mitochondrial fuel preference rather than ATP-synthesizing respiration. As such, therapies targeting fuel preference might be more suitable for treating NAFLD. Similarly, suppressing maladaptive antioxidants, rather than interfering with physiological mitochondrial H
Identifiants
pubmed: 33276146
pii: S2212-8778(20)30208-8
doi: 10.1016/j.molmet.2020.101134
pmc: PMC8324685
pii:
doi:
Substances chimiques
Blood Glucose
0
Hypoglycemic Agents
0
Insulin
0
Hydrogen Peroxide
BBX060AN9V
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
101134Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK041301
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026914
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
Références
Cell Metab. 2013 Apr 2;17(4):491-506
pubmed: 23562075
Diabetologia. 2016 Dec;59(12):2632-2644
pubmed: 27628106
Cell Metab. 2018 Oct 2;28(4):588-604.e5
pubmed: 30017357
Cell Metab. 2011 Dec 7;14(6):804-10
pubmed: 22152305
Nat Med. 2016 Aug;22(8):879-88
pubmed: 27400265
Hepatology. 2017 May;65(5):1543-1556
pubmed: 28027586
Hepatol Res. 2014 Sep;44(9):1026-36
pubmed: 24299564
JCI Insight. 2019 Apr 23;5:
pubmed: 31012869
Nature. 2008 Dec 4;456(7222):605-10
pubmed: 19052620
Hepatology. 2014 Jun;59(6):2178-87
pubmed: 24777953
J Biol Chem. 2018 Nov 2;293(44):17208-17217
pubmed: 30232152
Biochem Biophys Res Commun. 2011 Sep 9;412(4):618-25
pubmed: 21856284
Diabetes Obes Metab. 2010 Oct;12 Suppl 2:116-25
pubmed: 21029308
Nat Commun. 2018 Apr 20;9(1):1581
pubmed: 29679077
Nat Metab. 2020 May;2(5):413-431
pubmed: 32478287
Cell Metab. 2015 May 5;21(5):739-46
pubmed: 25955209
Nat Med. 2014 Dec;20(12):1427-35
pubmed: 25419710
Cell. 2019 May 2;177(4):881-895.e17
pubmed: 31051106
Physiol Rev. 2009 Jul;89(3):799-845
pubmed: 19584314
Sci Transl Med. 2019 Oct 2;11(512):
pubmed: 31578240
EMBO J. 2008 Jan 23;27(2):433-46
pubmed: 18200046
Biochim Biophys Acta. 2008 Nov;1780(11):1273-90
pubmed: 18267127
Hepatology. 2016 Jun;63(6):1987-2003
pubmed: 26845758
Cell. 2010 May 14;141(4):656-67
pubmed: 20478256
Hepatology. 2015 Mar;61(3):870-82
pubmed: 25179419
Cell Metab. 2015 Oct 6;22(4):682-94
pubmed: 26344101
Nat Commun. 2020 May 14;11(1):2397
pubmed: 32409697
Mol Metab. 2017 Nov;6(11):1468-1479
pubmed: 29107293
J Cell Biol. 2016 Jul 4;214(1):25-34
pubmed: 27377248
Adv Med Sci. 2018 Mar;63(1):68-78
pubmed: 28822266
Cell Death Dis. 2014 Apr 17;5:e1179
pubmed: 24743734
Cell Metab. 2018 Apr 3;27(4):869-885.e6
pubmed: 29617645
Free Radic Biol Med. 2012 Mar 1;52(5):841-9
pubmed: 22210379
J Biol Chem. 2009 Feb 20;284(8):5352-61
pubmed: 19049983
Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15803-8
pubmed: 18838687
Hepatology. 2019 Dec;70(6):1972-1985
pubmed: 31081165
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16093-8
pubmed: 12456881
Liver Int. 2016 Jan;36(1):5-20
pubmed: 26436447
Adv Healthc Mater. 2019 Jun;8(12):e1801511
pubmed: 30698920
J Lipid Res. 2018 Oct;59(10):1977-1986
pubmed: 30042157
Obesity (Silver Spring). 2019 Apr;27(4):612-620
pubmed: 30768775
J Lipid Res. 2020 Jan;61(1):10-19
pubmed: 31719103
Nature. 2012 Dec 13;492(7428):261-5
pubmed: 23172144
Metabolism. 1981 Dec;30(12):1170-8
pubmed: 6273686
Blood. 2012 Feb 9;119(6):1490-500
pubmed: 22144182
Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5523-8
pubmed: 22427360
Metabolism. 1991 Nov;40(11):1185-90
pubmed: 1943747
Diabetes. 1980 Mar;29(3):236-40
pubmed: 7380110
FEBS Lett. 1997 Oct 13;416(1):15-8
pubmed: 9369223
Adv Enzyme Regul. 1968;6:3-30
pubmed: 5720339
Medicine (Baltimore). 2017 Dec;96(49):e9061
pubmed: 29245314
Mol Metab. 2020 Nov;41:101051
pubmed: 32653576
Nature. 2009 Apr 30;458(7242):1131-5
pubmed: 19339967
J Clin Invest. 2020 Mar 2;130(3):1453-1460
pubmed: 31805015
Science. 2016 Jan 15;351(6270):275-281
pubmed: 26816379
Cell Metab. 2008 Jan;7(1):45-56
pubmed: 18177724
FASEB J. 2019 Mar;33(3):4154-4165
pubmed: 30550357
JCI Insight. 2018 Jun 21;3(12):
pubmed: 29925686
BMJ. 2010 Nov 04;341:c5702
pubmed: 21051774
Nutrients. 2018 Jul 27;10(8):
pubmed: 30060482
Cell Rep. 2019 Jan 2;26(1):192-208.e6
pubmed: 30605676
Science. 1992 Oct 30;258(5083):766-70
pubmed: 1439783
Cell Rep. 2017 Oct 3;21(1):1-9
pubmed: 28978464
J Clin Invest. 2015 Dec;125(12):4447-62
pubmed: 26571396
EMBO J. 2013 Aug 28;32(17):2348-61
pubmed: 23921556
Science. 2015 Mar 13;347(6227):1253-6
pubmed: 25721504
Free Radic Biol Med. 2016 Jan;90:12-23
pubmed: 26577173
Biochem J. 1985 Oct 15;231(2):439-44
pubmed: 4062906
Hepatology. 2015 Feb;61(2):486-96
pubmed: 25203315
Biochem Pharmacol. 1987 Oct 1;36(19):3231-6
pubmed: 3663237
Ann Hepatol. 2017 Aug 1;16(4):538-547
pubmed: 28611274
Gastroenterology. 2010 Sep;139(3):846-56, 856.e1-6
pubmed: 20685204
Cell Metab. 2013 Nov 5;18(5):740-8
pubmed: 24206666
Cell Metab. 2018 Nov 6;28(5):776-786.e5
pubmed: 30122556
Redox Biol. 2019 Feb;21:101120
pubmed: 30708325
Cell. 2014 Jul 3;158(1):25-40
pubmed: 24995976
EMBO J. 2014 Mar 3;33(5):418-36
pubmed: 24431221
Hepatol Commun. 2020 May 21;4(7):953-972
pubmed: 32626829
Cell Metab. 2017 Sep 5;26(3):576
pubmed: 28877461
Diabetologia. 2013 Oct;56(10):2286-96
pubmed: 23832083
Cell. 2019 May 30;177(6):1536-1552.e23
pubmed: 31150623
J Biol Chem. 1969 Dec 10;244(23):6403-14
pubmed: 4982202
Hepatology. 2003 Oct;38(4):999-1007
pubmed: 14512887
Diabetes. 2009 Mar;58(3):590-9
pubmed: 19074988
Int J Mol Sci. 2018 Sep 19;19(9):
pubmed: 30235785
Diabetes Care. 2018 Jun;41(6):1235-1243
pubmed: 29602794
Mol Endocrinol. 2015 Oct;29(10):1414-25
pubmed: 26296152
Vet Hum Toxicol. 2004 Oct;46(5):251-4
pubmed: 15487646
Cell Metab. 2009 Oct;10(4):260-72
pubmed: 19808019
Life Sci. 2008 May 23;82(21-22):1070-6
pubmed: 18448125
Front Pediatr. 2019 Nov 07;7:458
pubmed: 31788461
J Biol Chem. 2004 Sep 3;279(36):37716-25
pubmed: 15192089
Mol Cell. 2012 Aug 24;47(4):547-57
pubmed: 22748923
Physiol Rev. 1997 Jul;77(3):731-58
pubmed: 9234964
Clin Gastroenterol Hepatol. 2014 Dec;12(12):2092-103.e1-6
pubmed: 24582567
Cell Chem Biol. 2019 Oct 17;26(10):1450-1460.e7
pubmed: 31353321
Int J Mol Sci. 2016 Jan 16;17(1):
pubmed: 26784190
Biomed Pharmacother. 2018 Jun;102:689-698
pubmed: 29604588
Clin Gastroenterol Hepatol. 2017 Dec;15(12):1940-1949.e8
pubmed: 28419855
Cell Metab. 2015 Oct 6;22(4):669-81
pubmed: 26344103
Cell Metab. 2014 Sep 2;20(3):512-25
pubmed: 25043817
J Lipid Res. 2014 Dec;55(12):2541-53
pubmed: 25271296
Am J Physiol Gastrointest Liver Physiol. 2014 Sep 15;307(6):G632-41
pubmed: 25080922
JAMA. 2011 Oct 12;306(14):1549-56
pubmed: 21990298
Cell Metab. 2014 Oct 7;20(4):678-86
pubmed: 25295788
Diabetes. 2016 Dec;65(12):3552-3560
pubmed: 27613809
Biochem Biophys Rep. 2017 Mar 13;11:174-181
pubmed: 28955782
Biochem J. 1986 Oct 1;239(1):103-8
pubmed: 3800970
J Med Toxicol. 2011 Sep;7(3):205-12
pubmed: 21739343
Eur J Pharmacol. 2019 Dec 1;864:172715
pubmed: 31593687
ACS Chem Biol. 2016 Aug 19;11(8):2177-85
pubmed: 27232847
Sci Rep. 2019 Jul 23;9(1):10663
pubmed: 31337855