Seipin oligomers can interact directly with AGPAT2 and lipin 1, physically scaffolding critical regulators of adipogenesis

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Seipin oligomers can interact directly with AGPAT2 and lipin 1, physically scaffolding critical regulators of adipogenesis

OBJECTIVE Disruption of the genes encoding either seipin or 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) causes severe congenital generalized lipodystrophy (CGL) in humans. However, the function of seipin in adipogenesis remains poorly defined. We demonstrated recently that seipin can bind the key adipogenic phosphatidic acid (PA) phosphatase lipin 1 and that seipin forms stable dode...

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Regulation of lipin-1 gene expression by glucocorticoids during adipogenesis.

Lipin-1 deficiency in the mouse causes generalized lipodystrophy, characterized by impaired adipose tissue development and insulin resistance. Lipin-1 expression in differentiating preadipocytes is required for normal expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma and CCAAT enhancer binding protein alpha, and for the synthesis of triac...

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Lipin proteins form homo- and hetero-oligomers.

Lipin family members (lipin 1, 2 and 3) are bi-functional proteins that dephosphorylate PA (phosphatidic acid) to produce DAG (diacylglycerol) and act in the nucleus to regulate gene expression. Although other components of the triacylglycerol synthesis pathway can form oligomeric complexes, it is unknown whether lipin proteins also exist as oligomers. In the present study, using various approa...

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BSCL2/seipin regulates adipogenesis through actin cytoskeleton remodelling.

Seipin regulates lipid homeostasis by preventing lipid droplet (LD) formation in non-adipocytes but promoting it in developing adipocytes. Here, we report that seipin interacts with 14-3-3β through its N- and C-termini. Expression of 14-3-3β is upregulated during adipogenesis, and its deletion results in defective adipogenesis without affecting key adipogenic transcription factors. We further i...

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Towards a mechanistic understanding of lipodystrophy and seipin functions

CGL (Congenital generalized lipodystrophy) is a genetic disorder characterized by near complete loss of adipose tissue along with increased ectopic fat storage in other organs including liver and muscle. Of the four CGL types, BSCL2 (Berardinelli-Seip Congenital lipodystrophy type 2), resulting from mutations in the BSCL2/seipin gene, exhibits the most severe lipodystrophic phenotype with loss ...

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ژورنال

عنوان ژورنال: Molecular Metabolism

سال: 2015

ISSN: 2212-8778

DOI: 10.1016/j.molmet.2014.12.013