Adipocyte-specific Beclin1 deletion impairs lipolysis and mitochondrial integrity in adipose tissue.
Adipocytes
/ metabolism
Adipose Tissue
/ metabolism
Adipose Tissue, Brown
/ metabolism
Animals
Autophagy
/ genetics
Beclin-1
/ genetics
Cell Line
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
/ metabolism
DNA Copy Number Variations
Gene Deletion
Immunity
Lipid Metabolism
Lipolysis
/ genetics
Mice
Mice, Knockout
Mitochondria
/ genetics
Mitochondrial Proteins
/ genetics
Receptors, Adrenergic, beta-3
/ metabolism
Signal Transduction
Thermogenesis
/ genetics
Beclin1
Brown adipose tissue
Lipolysis
Lipophagy
Mitophagy
White adipose tissue
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
26
02
2020
revised:
10
04
2020
accepted:
16
04
2020
pubmed:
29
4
2020
medline:
9
7
2021
entrez:
29
4
2020
Statut:
ppublish
Résumé
Beclin1 is a core molecule of the macroautophagy machinery. Although dysregulation of macroautophagy is known to be involved in metabolic disorders, the function of Beclin1 in adipocyte metabolism has not been investigated. In the present study, we aimed to study the role of Beclin1 in lipolysis and mitochondrial homeostasis of adipocytes. Autophagic flux during lipolysis was examined in adipocytes cultured in vitro and in the adipose tissue of mice. Adipocyte-specific Beclin1 knockout (KO) mice were used to investigate the activities of Beclin1 in adipose tissues. cAMP/PKA signaling increased the autophagic flux in adipocytes differentiated from C3H10T1/2 cells. In vivo autophagic flux was higher in the brown adipose tissue (BAT) than that in the white adipose tissue and was further increased by the β3 adrenergic receptor agonist CL316243. In addition, surgical denervation of BAT greatly reduced autophagic flux, indicating that sympathetic nerve activity is a major regulator of tissue autophagy. Adipocyte-specific KO of Beclin1 led to a hypertrophic enlargement of lipid droplets in BAT and impaired CL316243-induced lipolysis/lipid mobilization and energy expenditure. While short-term effects of Beclin1 deletion were characterized by an increase in mitochondrial proteins, long-term Beclin1 deletion led to severe disruption of autophagy, resulting in mitochondrial loss, and dramatically reduced the expression of genes involved in lipid metabolism. Consequently, adipose tissue underwent increased activation of cell death signaling pathways, macrophage recruitment, and inflammation, particularly in BAT. The present study demonstrates the critical roles of Beclin1 in the maintenance of lipid metabolism and mitochondrial homeostasis in adipose tissues.
Identifiants
pubmed: 32344065
pii: S2212-8778(20)30079-X
doi: 10.1016/j.molmet.2020.101005
pmc: PMC7235646
pii:
doi:
Substances chimiques
Beclin-1
0
Mitochondrial Proteins
0
Receptors, Adrenergic, beta-3
0
Cyclic AMP
E0399OZS9N
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
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
101005Subventions
Organisme : NIDDK NIH HHS
ID : F31 DK116536
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062292
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
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