RT Journal Article
T1 Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning
A1 Pellegrini, Camilla
A1 Columbaro, Marta
A1 Schena, Elisa
A1 Prencipe, Sabino
A1 Andrenacci, Davide
A1 Iozzo, Patricia
A1 Guzzardi, Maria Angela
A1 Capanni, Cristina
A1 Mattioli, Elisabetta
A1 Loi, Manuela
A1 Araujo-Vilar, David
A1 Squarzoni, Stefano
A1 Cinti, Saverio
A1 Morselli, Paolo
A1 Giorgetti, Assuero
A1 Zanotti, Laura
A1 Gambineri, Alessandra
A1 Lattanzi, Giovanna
AB Type-2 Familial Partial Lipodystrophy is caused by LMNA mutations. Patients gradually lose subcutaneous fat from thelimbs, while they accumulate adipose tissue in the face and neck. Several studies have demonstrated that autophagy isinvolved in the regulation of adipocyte differentiation and the maintenance of the balance between white and brownadipose tissue. We identified deregulation of autophagy in laminopathic preadipocytes before induction ofdifferentiation. Moreover, in differentiating white adipocyte precursors, we observed impairment of large lipid dropletformation, 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. Inagreement 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 itsbrown origin. Moreover, in vivo morpho-functional evaluation of fat depots in the neck area of three FPLD2 patients byPET/CT analysis with cold stimulation showed the absence of brown adipose tissue activity. These findings highlight anew pathogenetic mechanism leading to improper fat distribution in lamin A-linked lipodystrophies and show thatboth impaired white adipocyte turnover and failure of adipose tissue browning contribute to disease.
SN 1226-3613
YR 2019
FD 2019-08-02
LK http://hdl.handle.net/10347/20929
UL http://hdl.handle.net/10347/20929
LA eng
NO Pellegrini, C., Columbaro, M., Schena, E. et al. Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning. Exp Mol Med 51, 1–17 (2019). https://doi.org/10.1038/s12276-019-0289-0
NO We thank FPLD2 patients for donating biological samples. We thank the ItalianNetwork for Laminopathies and the European Consortium of Lipodystrophies(ECLip) for support and helpful discussion. We thank Aurelio Valmori for thetechnical support. The studies were supported by Rizzoli Orthopedic Institute“5 per mille” 2014 project to MC, AIProSaB project 2016 and Fondazione DelMonte di Bologna e Ravenna grant 2015–2016 “New pharmacologicalapproaches in bone laminopathies based on the use of antibodies neutralizingTGF beta 2” to GL. GL is also supported by PRIN MIUR project 2015FBNB5Y.
DS Minerva
RD 27 abr 2026