Perilipins 2 and 3 lack a carboxy-terminal domain present in perilipin 1 involved in sequestering ABHD5 and suppressing basal lipolysis

Abstract

Lipid droplets (LDs) are a conserved feature of most organisms. Vertebrate adipocytes have evolved to efficiently store and release lipids for the whole organism from a single droplet. Perilipin 1, the most abundant lipid-coat protein in adipocytes, plays a key role in regulating lipolysis. In other tissues such as liver and muscle, LDs serve very different biological functions, buffering surplus lipids for subsequent oxidation or export. These tissues express perilipins 2 or 3, rather than perilipin 1. We sought to understand the role of perilipins 2 and 3 in regulating basal lipolysis. Bimolecular fluorescence complementation studies suggested that whereas perilipin 1 prevents the activation of adipose tissue triacylglycerol lipase by its coactivator, AB-hydrolase domain containing-5 (ABHD5), perilipins 2 and 3 do so less effectively. These differences are mediated by a conserved region within the carboxy terminus of perilipin 1 that binds and stabilizes ABHD5 by retarding its degradation by the proteosome. Chimeric proteins generated by fusing the carboxy terminus of perilipin 1 to the amino terminus of perilipins 2 or 3 stabilize ABHD5 and suppress basal lipolysis more effectively than WT perilipins 2 or 3. Furthermore, knockdown of perilipin 1 in adipocytes leads to replacement of perilipin 2 on LDs. In these cells we observed reduced ABHD5 expression and LD localization and a corresponding increase in basal lipolysis. Collectively these data suggest that whereas perilipin 1 potently suppresses basal lipolysis in adipocytes, perilipins 2 and 3 facilitate higher rates of basal lipolysis in other tissues where constitutive traffic of fatty acids via LDs is a necessary step in their metabolism.

Annual life-stage regulation of lipid metabolism and storage and association with PPARs in the migrant species Gray Catbird (Dumetella carolinensis)

“…We found no significant variation in perilipin-1 (PLIN1) gene expression, but perilipin-3 (PLIN3) gene expression was significantly elevated during pre-migratory stages. As PLIN3 is less effective at preventing lipolysis than PLIN1 (Patel et al, 2014), a greater proportion of PLIN3 on the lipid droplets favors lipid mobilization. However, there was no correlation between PLIN3 expression and lipid release from adipose tissue.…”

“…Gray catbirds, D. carolinensis (Linnaeus 1766), were captured with mist nets from 30 April to 11 May (late spring migration), 11 to 27 June (breeding), 5 to 15 August ( pre-migration) and 17 to 27 September (early autumn migration) in and 2014, and 8 to 16 January in 2014 Upon capture, all birds were weighed and birds in Ohio were analyzed for whole-body composition using an EchoMRISuperFLEX™ analyzer (EchoMRI, Houston, TX, USA). All birds were then killed with an isofluorane overdose and decapitated.…”

The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis

“…LDs are heterogeneous in their coats, and LD proteins generally demonstrate tissuespecific distribution patterns (9). In healthy murine liver, Perilipin 2 and Perilipin 3 promote LD formation (10), whereas Cideb promotes VLDL lipidation (11). Although deletion of Perilipin 3 has not yet been performed, genetic deletion of Perilipin 2 or Cideb ameliorates hepatic steatosis (12,13).…”

Role of Lipid Droplet Proteins in the Development of NAFLD and Hepatic Insulin Resistance

“…Four-helix bundle in PLIN3 has been suggested to contribute to faty acid binding and lipid droplet recruitment [9]. PLIN2 and PLIN3 share similar functions, and both proteins cannot bind CGI-58 and, therefore, inluence lipolysis [27]. Co-expression of PLIN2 and PLIN3 has been reported in many tissues; however, a distinct role of PLIN3 has not been clearly identiied.…”