Primary cilia-dependent lipid raft/caveolin dynamics regulate adipogenesis.
Adipogenesis
/ drug effects
Animals
Aurora Kinase A
/ antagonists & inhibitors
Carrier Proteins
/ antagonists & inhibitors
Caveolin 1
/ metabolism
Cilia
/ metabolism
Energy Metabolism
Insulin
/ pharmacology
Membrane Microdomains
/ metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
/ metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt
/ metabolism
RNA Interference
RNA, Small Interfering
/ metabolism
Receptor, IGF Type 1
/ genetics
Signal Transduction
Akt
adipogenesis
caveolae
ciliary base
insulin signaling
lipid rafts
obesity
primary cilia
trichoplein
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 03 2021
09 03 2021
Historique:
received:
15
09
2020
revised:
28
12
2020
accepted:
11
02
2021
entrez:
10
3
2021
pubmed:
11
3
2021
medline:
27
1
2022
Statut:
ppublish
Résumé
Primary cilia play a pivotal role in signal transduction and development and are known to serve as signaling hubs. Recent studies have shown that primary cilium dysfunction influences adipogenesis, but the mechanisms are unclear. Here, we show that mesenchymal progenitors C3H10T1/2 depleted of trichoplein, a key regulator of cilium formation, have significantly longer cilia than control cells and fail to differentiate into adipocytes. Mechanistically, the elongated cilia prevent caveolin-1- and/or GM3-positive lipid rafts from being assembled around the ciliary base where insulin receptor proteins accumulate, thereby inhibiting the insulin-Akt signaling. We further generate trichoplein knockout mice, in which adipogenic progenitors display elongated cilia and impair the lipid raft dynamics. The knockout mice on an extended high-fat diet exhibit reduced body fat and smaller adipocytes than wild-type (WT) mice. Overall, our results suggest a role for primary cilia in regulating adipogenic signal transduction via control of the lipid raft dynamics around cilia.
Identifiants
pubmed: 33691104
pii: S2211-1247(21)00131-5
doi: 10.1016/j.celrep.2021.108817
pii:
doi:
Substances chimiques
Carrier Proteins
0
Caveolin 1
0
Igf1r protein, mouse
0
Insulin
0
RNA, Small Interfering
0
Receptor, IGF Type 1
EC 2.7.10.1
Aurka protein, mouse
EC 2.7.11.1
Aurora Kinase A
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
108817Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.