Single-Cell RNA Profiling Reveals Adipocyte to Macrophage Signaling Sufficient to Enhance Thermogenesis.
Adipocytes, Beige
/ metabolism
Adipose Tissue, Brown
/ metabolism
Adipose Tissue, White
/ metabolism
Animals
Cell Polarity
Cold Temperature
Cyclic AMP
/ metabolism
Denervation
Fatty Acid Synthases
/ metabolism
Macrophage Activation
Macrophages
/ metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Neuregulins
/ deficiency
Phenotype
RNA
/ metabolism
Signal Transduction
Single-Cell Analysis
Thermogenesis
Uncoupling Protein 1
/ genetics
Up-Regulation
/ genetics
beige adipocytes
de novo lipogenesis
macrophage polarization
stromal vascular fraction
sympathetic nerve fibers
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
received:
05
05
2020
revised:
22
06
2020
accepted:
15
07
2020
entrez:
7
8
2020
pubmed:
7
8
2020
medline:
4
5
2021
Statut:
ppublish
Résumé
Adipocytes deficient in fatty acid synthase (iAdFASNKO) emit signals that mimic cold exposure to enhance the appearance of thermogenic beige adipocytes in mouse inguinal white adipose tissues (iWATs). Both cold exposure and iAdFASNKO upregulate the sympathetic nerve fiber (SNF) modulator Neuregulin 4 (Nrg4), activate SNFs, and require adipocyte cyclic AMP/protein kinase A (cAMP/PKA) signaling for beige adipocyte appearance, as it is blocked by adipocyte Gsα deficiency. Surprisingly, however, in contrast to cold-exposed mice, neither iWAT denervation nor Nrg4 loss attenuated adipocyte browning in iAdFASNKO mice. Single-cell transcriptomic analysis of iWAT stromal cells revealed increased macrophages displaying gene expression signatures of the alternately activated type in iAdFASNKO mice, and their depletion abrogated iWAT beiging. Altogether, these findings reveal that divergent cellular pathways are sufficient to cause adipocyte browning. Importantly, adipocyte signaling to enhance alternatively activated macrophages in iAdFASNKO mice is associated with enhanced adipose thermogenesis independent of the sympathetic neuron involvement this process requires in the cold.
Identifiants
pubmed: 32755590
pii: S2211-1247(20)30983-9
doi: 10.1016/j.celrep.2020.107998
pmc: PMC7433376
mid: NIHMS1617897
pii:
doi:
Substances chimiques
Neuregulins
0
Uncoupling Protein 1
0
neuregulin-4
0
RNA
63231-63-0
Cyclic AMP
E0399OZS9N
Fatty Acid Synthases
EC 2.3.1.85
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107998Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK116056
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK120649
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK089503
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI147868
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK102456
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020541
Pays : United States
Organisme : NIDDK NIH HHS
ID : R37 DK030898
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK030898
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK103047
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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