The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation

Weiqin Chen, Vijay K. Yechoor, Benny Hung Junn Chang, Ming V. Li, Keith L. March, Lawrence Chan

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Mutations in the Berardinelli-Seip congenital lipodystrophy 2 gene (BSCL2) are the underlying defect in patients with congenital generalized lipodystrophy type 2. BSCL2 encodes a protein called seipin, whose function is largely unknown. In this study, we investigated the role of Bscl2 in the regulation of adipocyte differentiation. Bscl2 mRNA is highly up-regulated during standard hormone-induced adipogenesis in 3T3-L1 cells in vitro. However, this up-regulation does not occur during mesenchymal stem cell (C3H10T1/2 cells) commitment to the preadipocyte lineage. Knockdown of Bscl2 by short hairpin RNA in C3H10T1/2 cells has no effect on bone morphogenetic protein-4-induced preadipocyte commitment. However, knockdown in 3T3-L1 cells prevents adipogenesis induced by a standard hormone cocktail, but adipogenesis can be rescued by the addition of peroxisome proliferator-activated receptor-γ agonist pioglitazone at an early stage of differentiation. Interestingly, pioglitazone-induced differentiation in the absence of standard hormone is not associated with up-regulated Bscl2 expression. On the other hand, short hairpin RNA-knockdown of Bscl2 largely blocks pioglitazone-induced adipose differentiation. These experiments suggest that Bscl2 may be essential for normal adipogenesis; it works upstream or at the level of peroxisome proliferator-activated receptor-γ, enabling the latter to exert its full activity during adipogenesis. Loss of Bscl2 function thus interferes with the normal transcriptional cascade of adipogenesis during fat cell differentiation, resulting in near total loss of fat or lipodystrophy.

Original languageEnglish
Pages (from-to)4552-4561
Number of pages10
JournalEndocrinology
Volume150
Issue number10
DOIs
StatePublished - Oct 2009

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Congenital Generalized Lipodystrophy
Lipodystrophy
Adipogenesis
pioglitazone
Adipocytes
Genes
3T3-L1 Cells
Peroxisome Proliferator-Activated Receptors
Hormones
Small Interfering RNA
Bone Morphogenetic Protein 4
Mesenchymal Stromal Cells
Cell Differentiation
Up-Regulation
Fats
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Endocrinology

Cite this

The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation. / Chen, Weiqin; Yechoor, Vijay K.; Chang, Benny Hung Junn; Li, Ming V.; March, Keith L.; Chan, Lawrence.

In: Endocrinology, Vol. 150, No. 10, 10.2009, p. 4552-4561.

Research output: Contribution to journalArticle

Chen, Weiqin ; Yechoor, Vijay K. ; Chang, Benny Hung Junn ; Li, Ming V. ; March, Keith L. ; Chan, Lawrence. / The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation. In: Endocrinology. 2009 ; Vol. 150, No. 10. pp. 4552-4561.
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