Regulated in Development and DNA Damage Responses 1 Prevents Dermal Adipocyte Differentiation and Is Required for Hair Cycle-Dependent Dermal Adipose Expansion.
3T3 Cells
Adipocytes
/ pathology
Adipogenesis
/ genetics
Animals
Cell Differentiation
/ genetics
Dermis
/ cytology
Disease Models, Animal
Female
Gene Expression Regulation, Developmental
Hair Follicle
/ growth & development
Humans
Hyperplasia
/ genetics
Hypertrophy
/ genetics
Male
Mice
Mice, Knockout
Signal Transduction
/ genetics
Subcutaneous Fat
/ cytology
Transcription Factors
/ genetics
Journal
The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
12
09
2019
revised:
14
11
2019
accepted:
04
12
2019
pubmed:
8
2
2020
medline:
2
4
2021
entrez:
8
2
2020
Statut:
ppublish
Résumé
Dermal white adipose tissue (dWAT) expansion is associated with important homeostatic and pathologic processes in skin. Even though mTOR/protein kinase B signaling is important for adipogenesis, the role of regulated development of DNA damage responses 1 (REDD1), a negative regulator of mTOR/protein kinase B, is poorly understood. Loss of REDD1 in mice resulted in reduction of body mass, total fat, size of gonadal white adipose tissue, and interscapular brown adipose tissue. Inguinal subcutaneous white adipose tissue and dWAT in REDD1 knockouts were expanded compared with wild type mice. Size and number of mature adipocytes in dWAT were also increased in adult REDD1 knockouts. This dWAT phenotype was established around postnatal day 18 and did not depend on the hair growth cycle. Numbers of adipocyte precursor cells were lower in REDD1 knockout skin. In vitro analysis revealed increased differentiation of skin-derived REDD1 knockout adipocyte precursor cells as indicated by higher lipid accumulation and increased adipogenic marker expression. 3T3L1 cells overexpressing REDD1 had decreased sensitivity to differentiation. Overall, our findings indicate that REDD1 silencing induced expansion of dWAT through hypertrophy and hyperplasia. This REDD1-dependent mechanism of adipogenesis could be used to preferentially target skin-associated adipose tissue for therapeutic purposes.
Identifiants
pubmed: 32032578
pii: S0022-202X(20)30130-5
doi: 10.1016/j.jid.2019.12.033
pmc: PMC7398827
mid: NIHMS1561206
pii:
doi:
Substances chimiques
Ddit4 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1698-1705.e1Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR057216
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM112945
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIAMS NIH HHS
ID : R56 AR060295
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125366
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR075412
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
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