Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase.
Adipocytes
/ enzymology
Age Factors
Animals
Blood Glucose
/ metabolism
Disease Models, Animal
Energy Metabolism
Fatty Liver
/ enzymology
Insulin
/ metabolism
Lipodystrophy
/ enzymology
Lipolysis
Liver
/ metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
PPAR gamma
/ metabolism
Sterol Esterase
/ deficiency
Time Factors
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
10 03 2021
10 03 2021
Historique:
received:
31
03
2020
accepted:
16
02
2021
entrez:
11
3
2021
pubmed:
12
3
2021
medline:
10
8
2021
Statut:
epublish
Résumé
Modulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.
Identifiants
pubmed: 33692445
doi: 10.1038/s42003-021-01858-z
pii: 10.1038/s42003-021-01858-z
pmc: PMC7946939
doi:
Substances chimiques
Blood Glucose
0
Insulin
0
PPAR gamma
0
Pparg protein, mouse
0
Sterol Esterase
EC 3.1.1.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
323Subventions
Organisme : Austrian Science Fund FWF
ID : I 3535
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 28882
Pays : Austria
Références
Nat Methods. 2011 Dec 28;9(1):57-63
pubmed: 22205519
Genes Dev. 2013 Mar 1;27(5):459-84
pubmed: 23475957
J Lipid Res. 2005 Nov;46(11):2347-55
pubmed: 16150820
J Hepatol. 2015 Aug;63(2):437-45
pubmed: 25733154
J Clin Invest. 2010 Oct;120(10):3466-79
pubmed: 20877011
Nat Commun. 2017 Mar 22;8:14859
pubmed: 28327588
J Biol Chem. 2006 Dec 29;281(52):40236-41
pubmed: 17074755
Endocrinology. 2015 Oct;156(10):3610-24
pubmed: 26196542
Diabetes. 2010 Feb;59(2):323-9
pubmed: 20103710
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13656-61
pubmed: 10570128
FASEB J. 2009 Jul;23(7):2307-16
pubmed: 19246492
Curr Opin Endocrinol Diabetes Obes. 2011 Apr;18(2):139-43
pubmed: 21297467
Adipocyte. 2014 Jul 1;3(3):206-11
pubmed: 25068087
Cell. 2015 Feb 12;160(4):745-758
pubmed: 25662011
PLoS One. 2008 Mar 12;3(3):e1793
pubmed: 18335062
Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1182-95
pubmed: 12954598
Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13850-5
pubmed: 26508640
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):787-92
pubmed: 10639158
Methods Enzymol. 2014;538:171-93
pubmed: 24529439
J Biol Chem. 2018 Sep 7;293(36):13974-13988
pubmed: 30042231
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11245-50
pubmed: 15266058
PLoS Biol. 2013;11(2):e1001485
pubmed: 23431266
Biochim Biophys Acta Mol Cell Biol Lipids. 2018 Feb;1863(2):212-218
pubmed: 29191637
J Biol Chem. 1957 May;226(1):497-509
pubmed: 13428781
J Nutr Biochem. 2011 Jun;22(6):543-53
pubmed: 20801631
J Biol Chem. 2003 Sep 5;278(36):34268-76
pubmed: 12805374
Biochim Biophys Acta. 2011 Jan;1811(1):9-16
pubmed: 20950707
J Lipid Res. 2003 Nov;44(11):2089-99
pubmed: 12923228
Nat Metab. 2019 Jan;1(1):133-146
pubmed: 32694809
J Biol Chem. 2002 Feb 15;277(7):4806-15
pubmed: 11717312
J Biol Chem. 2006 Dec 8;281(49):37603-15
pubmed: 16971390
Cell Metab. 2006 May;3(5):309-19
pubmed: 16679289
J Lipid Res. 2014 Nov;55(11):2276-86
pubmed: 25193997
Cell Metab. 2011 Jun 8;13(6):739-48
pubmed: 21641555
J Clin Invest. 2003 Mar;111(5):737-47
pubmed: 12618528
PLoS Genet. 2017 Dec 12;13(12):e1007110
pubmed: 29232702
PLoS Biol. 2020 Jul 14;18(7):e3000411
pubmed: 32663221
N Engl J Med. 2014 Jun 12;370(24):2307-2315
pubmed: 24848981
Cell Metab. 2011 Mar 2;13(3):249-59
pubmed: 21356515