Brain leptin reduces liver lipids by increasing hepatic triglyceride secretion and lowering lipogenesis.
Animals
Blood-Brain Barrier
/ metabolism
Diet, High-Fat
/ adverse effects
Disease Models, Animal
Humans
Infusions, Intraventricular
Injections, Intraventricular
Leptin
/ administration & dosage
Lipogenesis
/ physiology
Lipoproteins, VLDL
Liver
/ innervation
Male
Medulla Oblongata
/ metabolism
Non-alcoholic Fatty Liver Disease
/ etiology
Polyethylene Glycols
/ administration & dosage
Rats
Rats, Sprague-Dawley
Stereotaxic Techniques
Sympathectomy
Triglycerides
/ metabolism
Vagus Nerve
/ physiology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 06 2019
20 06 2019
Historique:
received:
07
11
2018
accepted:
24
05
2019
entrez:
22
6
2019
pubmed:
22
6
2019
medline:
10
7
2019
Statut:
epublish
Résumé
Hepatic steatosis develops when lipid influx and production exceed the liver's ability to utilize/export triglycerides. Obesity promotes steatosis and is characterized by leptin resistance. A role of leptin in hepatic lipid handling is highlighted by the observation that recombinant leptin reverses steatosis of hypoleptinemic patients with lipodystrophy by an unknown mechanism. Since leptin mainly functions via CNS signaling, we here examine in rats whether leptin regulates hepatic lipid flux via the brain in a series of stereotaxic infusion experiments. We demonstrate that brain leptin protects from steatosis by promoting hepatic triglyceride export and decreasing de novo lipogenesis independently of caloric intake. Leptin's anti-steatotic effects are generated in the dorsal vagal complex, require hepatic vagal innervation, and are preserved in high-fat-diet-fed rats when the blood brain barrier is bypassed. Thus, CNS leptin protects from ectopic lipid accumulation via a brain-vagus-liver axis and may be a therapeutic strategy to ameliorate obesity-related steatosis.
Identifiants
pubmed: 31222048
doi: 10.1038/s41467-019-10684-1
pii: 10.1038/s41467-019-10684-1
pmc: PMC6586634
doi:
Substances chimiques
Leptin
0
Lipoproteins, VLDL
0
Triglycerides
0
Polyethylene Glycols
3WJQ0SDW1A
tyloxapol
Y27PUL9H56
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
2717Subventions
Organisme : NIDDK NIH HHS
ID : R03 DK082724
Pays : United States
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 634413
Pays : International
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK026687
Pays : United States
Organisme : Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)
ID : P26766
Pays : International
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 722619
Pays : International
Organisme : Austrian Science Fund FWF
ID : P 26766
Pays : Austria
Organisme : NIDDK NIH HHS
ID : K08 DK074873
Pays : United States
Références
N Engl J Med. 2004 Mar 18;350(12):1220-34
pubmed: 15028826
Cell Metab. 2011 Feb 2;13(2):183-94
pubmed: 21284985
Diabetes. 2008 Jun;57(6):1482-90
pubmed: 18332095
Endocrinology. 2006 May;147(5):2088-94
pubmed: 16469809
Nature. 2002 Jan 17;415(6869):339-43
pubmed: 11797013
JAMA. 1999 Oct 27;282(16):1568-75
pubmed: 10546697
N Engl J Med. 2007 Jan 11;356(2):148-56
pubmed: 17215532
Diabetes. 2016 Jun;65(6):1511-20
pubmed: 26861781
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R868-74
pubmed: 17023670
J Pharmacol Exp Ther. 2010 Apr;333(1):253-63
pubmed: 20053933
Endocrinology. 2007 Dec;148(12):5604-10
pubmed: 17823267
Diabetes. 2011 Jun;60(6):1647-56
pubmed: 21617185
Endocrinology. 2012 Jan;153(1):143-53
pubmed: 22128019
J Biol Chem. 2004 May 21;279(21):21695-700
pubmed: 14993225
Annu Rev Nutr. 2000;20:663-97
pubmed: 10940349
J Lipid Res. 2002 Nov;43(11):1899-907
pubmed: 12401889
Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8878-83
pubmed: 9238071
Diabetes. 2012 May;61(5):1043-50
pubmed: 22461566
J Control Release. 2014 Oct 10;191:34-46
pubmed: 24881856
Diabetes. 2015 Jun;64(6):1966-75
pubmed: 25576060
Diabetes. 2004 Oct;53(10):2529-34
pubmed: 15448080
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13100-5
pubmed: 19622746
FEBS Lett. 1996 Aug 26;392(2):87-90
pubmed: 8772180
Endocrinology. 2007 Aug;148(8):3987-97
pubmed: 17495001
Compr Physiol. 2013 Apr;3(2):655-65
pubmed: 23720325
Diabetes. 2002 Oct;51(10):3025-32
pubmed: 12351443
Diabetes Care. 2016 Jan;39(1):92-100
pubmed: 26577417
J Neurosci. 2011 Aug 24;31(34):12189-97
pubmed: 21865462
Am J Physiol. 1990 Nov;259(5 Pt 1):G781-5
pubmed: 2240220
Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14795-9
pubmed: 8962134
J Clin Endocrinol Metab. 1998 Jun;83(6):1893-9
pubmed: 9626115
Hepatology. 2000 Nov;32(5):1045-9
pubmed: 11050055
J Clin Invest. 1999 May;103(9):1287-98
pubmed: 10225972
Diabetologia. 2016 Jan;59(1):30-43
pubmed: 26407715
Peptides. 1996;17(2):305-11
pubmed: 8801538
Cell Metab. 2006 Jul;4(1):49-60
pubmed: 16814732
Gastroenterology. 2008 Feb;134(2):424-31
pubmed: 18242210
Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1454-64
pubmed: 9261280
J Lipid Res. 2010 May;51(5):1057-62
pubmed: 20008831
Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11848-53
pubmed: 12195019
Nat Med. 2008 Jun;14(6):667-75
pubmed: 18516053
Liver. 1998 Oct;18(5):352-9
pubmed: 9831365
Cell Metab. 2008 Jan;7(1):45-56
pubmed: 18177724
Am J Gastroenterol. 2012 Dec;107(12):1852-8
pubmed: 23032980
J Clin Invest. 2005 Dec;115(12):3484-93
pubmed: 16284652
Int J Obes Relat Metab Disord. 1998 Aug;22(8):728-33
pubmed: 9725631
FASEB J. 2007 Jan;21(1):53-60
pubmed: 17099068
J Pharmacol Exp Ther. 1976 Sep;198(3):562-7
pubmed: 978459
J Clin Invest. 2002 May;109(10):1345-50
pubmed: 12021250
Nat Commun. 2015 Jan 12;6:5970
pubmed: 25580573
N Engl J Med. 2002 Feb 21;346(8):570-8
pubmed: 11856796
Diabetes Metab Res Rev. 2018 Nov;34(8):e3050
pubmed: 30052309
J Clin Invest. 2001 Oct;108(8):1113-21
pubmed: 11602618
Peptides. 1999 Nov;20(11):1341-5
pubmed: 10612449
Diabetes. 2000 Jul;49(7):1219-23
pubmed: 10909981
J Clin Invest. 2004 Feb;113(3):414-24
pubmed: 14755338
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6231-5
pubmed: 8692797
Diabetes. 2014 Apr;63(4):1422-7
pubmed: 24379349
J Clin Invest. 2008 Jun;118(6):2347-64
pubmed: 18497885
Nat Med. 2005 Mar;11(3):320-7
pubmed: 15735652
J Clin Invest. 2018 Aug 1;128(8):3504-3516
pubmed: 29723161
J Clin Invest. 2000 Jun;105(12):1827-32
pubmed: 10862798
J Lipid Res. 2003 Mar;44(3):470-8
pubmed: 12562873
J Clin Invest. 2017 Feb 1;127(2):657-669
pubmed: 28112679
Nat Med. 2007 Feb;13(2):171-80
pubmed: 17273170
Metabolism. 2004 Apr;53(4):513-9
pubmed: 15045701
Diabetes. 2011 May;60(5):1474-7
pubmed: 21411512
Am J Physiol. 1998 Feb;274(2):E321-7
pubmed: 9486165