Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.
Adipocytes
/ pathology
Adipocytes, Brown
/ physiology
Adipogenesis
/ physiology
Adipose Tissue, Brown
/ metabolism
Adult
Autophagy
/ physiology
Cell Differentiation
Cell Transdifferentiation
/ physiology
Cells, Cultured
Female
Humans
Lipodystrophy, Familial Partial
/ metabolism
Middle Aged
Young Adult
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
02 08 2019
02 08 2019
Historique:
received:
15
01
2018
accepted:
16
04
2019
revised:
04
04
2019
entrez:
4
8
2019
pubmed:
4
8
2019
medline:
30
5
2020
Statut:
epublish
Résumé
Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from the limbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy is involved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brown adipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction of differentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid droplet formation, altered regulation of adipose tissue genes, and expression of the brown adipose tissue marker UCP1. Conversely, in lipodystrophic brown adipocyte precursors induced to differentiate, we noticed activation of autophagy, formation of enlarged lipid droplets typical of white adipocytes, and dysregulation of brown adipose tissue genes. In agreement with these in vitro results indicating conversion of FPLD2 brown preadipocytes toward the white lineage, adipose tissue from FPLD2 patient neck, an area of brown adipogenesis, showed a white phenotype reminiscent of its brown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients by PET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight a new pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show that both impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.
Identifiants
pubmed: 31375660
doi: 10.1038/s12276-019-0289-0
pii: 10.1038/s12276-019-0289-0
pmc: PMC6802660
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-17Subventions
Organisme : Istituto Ortopedico Rizzoli di Bologna (Istituto Ortopedico Rizzoli)
ID : 5 per 1000 2014
Pays : International
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