期刊
MOLECULAR METABOLISM
卷 2, 期 1, 页码 38-46出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2012.11.002
关键词
Seipin; Adipogenesis; Lipodystrophy; Lipin; Endoplasmic reticulum
资金
- Medical Research Council (MRC) [G0800203, G0701446, G09000554]
- Swiss National Science Foundation [PBBEP3-123654/PA00P3-129106]
- Wellcome Trust [078986/Z/06/Z]
- Agency for Science, Technology and Research, Singapore(A*STAR)
- MRC Centre for Obesity and Related Metabolic Disorders (MRC-CORD) [G0600717]
- National Institute for Health Research Comprehensive Biomedical Research Centre [CG50826]
- Wellcome Trust [078986/Z/06/Z] Funding Source: Wellcome Trust
- MRC [G0600717, G0800203, G0701446] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [23591254] Funding Source: KAKEN
- Medical Research Council [G0600717B, G0701446, G0600717, G0800203] Funding Source: researchfish
Disruption of the gene BSCL2 causes a severe, generalised lipodystrophy, demonstrating the critical role of its protein product, seipin, in human adipose tissue development. Seipin is essential for adipocyte differentiation, whilst the study of seipin in non-adipose cells has suggested a role in lipid droplet formation. However, its precise molecular function remains poorly understood. Here we demonstrate that seipin can inducibly bind lipin 1, a phosphatidic acid (PA) phosphatase important for lipid synthesis and adipogenesis. Knockdown of seipin during early adipogenesis decreases the association of lipin 1 with membranes and increases the accumulation of its substrate PA. Conversely, PA levels are reduced in differentiating cells by overexpression of wild-type seipin but not by expression of a mutated seipin that is unable to bind lipin 1. Together our data identify lipin as the first example of a seipin-interacting protein and reveals a novel molecular function for seipin in developing adipocytes. Crown Copyright (C) 2012 Published by Elsevier GmbH.
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