Perilipin-related protein regulates lipid metabolism in C. elegans

PeerJ. 2015 Sep 1;3:e1213. doi: 10.7717/peerj.1213. eCollection 2015.

Abstract

Perilipins are lipid droplet surface proteins that contribute to fat metabolism by controlling the access of lipids to lipolytic enzymes. Perilipins have been identified in organisms as diverse as metazoa, fungi, and amoebas but strikingly not in nematodes. Here we identify the protein encoded by the W01A8.1 gene in Caenorhabditis elegans as the closest homologue and likely orthologue of metazoan perilipin. We demonstrate that nematode W01A8.1 is a cytoplasmic protein residing on lipid droplets similarly as human perilipins 1 and 2. Downregulation or elimination of W01A8.1 affects the appearance of lipid droplets resulting in the formation of large lipid droplets localized around the dividing nucleus during the early zygotic divisions. Visualization of lipid containing structures by CARS microscopy in vivo showed that lipid-containing structures become gradually enlarged during oogenesis and relocate during the first zygotic division around the dividing nucleus. In mutant embryos, the lipid containing structures show defective intracellular distribution in subsequent embryonic divisions and become gradually smaller during further development. In contrast to embryos, lipid-containing structures in enterocytes and in epidermal cells of adult animals are smaller in mutants than in wild type animals. Our results demonstrate the existence of a perilipin-related regulation of fat metabolism in nematodes and provide new possibilities for functional studies of lipid metabolism.

Keywords: Caenorhabditis elegans; Fat metabolism; Lipid droplets; Perilipin; Perilipin-related protein in C. elegans.

Grant support

This work was supported by the European Regional Development Fund “BIOCEV—Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec” (CZ.1.05/1.1.00/02.0109); the grant PRVOUK-P27/LF1/1 from Charles University in Prague; the grants SVV 260023/2014 and SVV 260149/2015 from Charles University in Prague. MWK is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, USA. The authors received funds from MediCentrum Praha a.s. to support the work reported in this publication. ZK and MK contributed personal funds to this work. The funders (excluding the authors) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.