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Sci Rep. 2016 Feb 15;6:20975. doi: 10.1038/srep20975.

Perilipin2 plays a positive role in adipocytes during lipolysis by escaping proteasomal degradation.

Author information

1
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
2
Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, Osaka, Japan.
3
The Center for Advanced Medical Engineering and Informatics, Osaka University, Osaka, Japan.

Abstract

Perilipin2 (Plin2), also known as adipose differentiation-related protein (ADRP), or adipophilin, is a member of the PAT family involved in lipid droplet (LD) formation in the liver and peripheral tissues. Although Plin2 was originally identified as a highly expressed gene in adipocytes, its physiological role in mature adipocytes is largely unknown. In this report, we investigated the regulation of Plin2 expression and its function in differentiated adipocytes of mouse embryonic fibroblasts (MEFs). Plin2 mRNA levels increased during adipocyte differentiation whereas protein levels did not. Plin2 was degraded through the ubiquitin-proteasome pathway but was inhibited by lipolytic inducers. Furthermore, lentiviral-mediated Plin2 knockdown attenuated lipolysis in differentiated MEFs in a time-dependent manner. Oleic acid-induced LD formation enhanced Plin2 protein stability when it was localized to LDs. Furthermore, a mutational analysis revealed that the ubiquitination and degradation of Plin2 required both the second and third alanine in the N-terminal region. These results suggest that Plin2 is degraded in the cytosol in its N-terminal amino acid sequence-dependent manner and instead becomes stable when localized on LDs. Our findings highlight the relationship between protein stability and a previously unnoticed function of Plin2 during lipolysis in adipocytes.

PMID:
26876687
PMCID:
PMC4753471
DOI:
10.1038/srep20975
[Indexed for MEDLINE]
Free PMC Article
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