PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Perilipin-1”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed2005

Drosophila Lipid Storage Droplet 2 gene (Lsd-2) is expressed and controls lipid storage in wing imaginal discs.

Lipid droplets are the major neutral lipid storage organelles in higher eukaryotes. The PAT domain proteins (Perilipin, ADRP [adipose differentiation related protein], and TIP47 [tail-interacting 47-kDa protein]) are associated with these structures. Perilipin and ADRP are involved in the regulation of lipid storage and metabolism in mammals. Two genes encoding PAT proteins, Drosophila Lipid Storage Droplet 2 Gene (Lsd-2) and Lsd-2, have been identified in Drosophila. Lsd-2 is expressed in fat bodies and in the female germ line and is involved in lipid storage in these tissues. We showed that Lsd-2 is expressed in third-instar wing imaginal discs in Drosophila, with higher levels in the wing pouch, which corresponds to the presumptive wing region of the wing disc. This specific expression pattern is correlated with a high level of neutral lipid accumulation. We also showed that neutral lipid deposition in the wing disc is severely reduced in an Lsd-2 mutant and is increased with Lsd-2 overexpression. Finally, we showed that overexpression of the vestigial (vg) pro-wing gene induces Lsd-2 expression, suggesting that Lsd-2 mediates a vg role during wing formation. Our results suggest that Lsd-2 function is not restricted to tissues directly involved in lipid storage and could play additional roles during development.

Animals↗
PubMed2002

Immunocytochemical studies on lipid droplet-surface proteins in adrenal cells.

Perilipin and ADRP, located on the surface of intracellular lipid droplets, are proposed to be involved in adipocyte lipid metabolism. The aim of the present study was to investigate the effect of PKA and PKC activities on the distribution of perilipin and ADRP in primary cultured adrenal cells, and the role of ERK in PMA- and calphostin C-induced steroidogenesis. Immunofluorescence staining indicated that in addition to p160, a capsular protein of steroidogenic lipid droplets, perilipin and ADRP were localized on the lipid droplet surface. Stimuli such as activation of PKA by db cAMP or inhibition of PKC by calphostin C, which increase corticosterone synthesis in various magnitudes, caused detachment of p160 and perilipin, but not ADRP, from the lipid droplet surface. Activation of PKC by PMA induced increase in corticosterone synthesis, however, it did not affect the distribution of perilipin, p160, or ADRP on the lipid droplet surface, suggesting the presence of mechanisms for promoting sterodiogensis other than causing detachment of lipid droplet surface proteins. We further demonstrated that ERK pathway was involved in PMA-induced steroidogenesis, since PD98059, specific inhibitor of MEK, blocked the increases in steroidogenesis and phosphorylation of ERK caused by PMA, but not by cAMP-PKA. These data indicate that p160, perilipin, and ADRP were all located on the lipid droplet surface in rat adrenal cells. On the basis of its non-responsiveness to lipolytic stimulation, ADRP may be a structural protein of the lipid droplet surface, whereas their immediate response to lipolytic stimuli suggest that perilipin and p160 are functional proteins. PKC regulates adrenal steroidogenesis through ERK cascade, whereas PKA pathway does not involve ERK.

Adrenal Glands↗
PubMed2003

TNF-alpha induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes.

Tumor necrosis factor-alpha (TNF-alpha) increases adipocyte lipolysis after 6-12 h of incubation. TNF-alpha has been demonstrated to activate mitogen-activated protein (MAP) kinases including extracellular signal-related kinase (ERK) and N-terminal-c-Jun-kinase (JNK) in different cell types. To determine if the MAP kinases have a role in TNF-alpha-induced lipolysis, 3T3-L1 adipocytes were treated with the cytokine (10 ng/ml), in the presence or absence of PD98059 or U0126 (100 micromoles), specific inhibitors of ERK activity. We demonstrated that U0126 or PD98059 blocked TNF-alpha-induced ERK activity and decreased TNF-alpha-induced lipolysis by 65 or 76% respectively. The peroxisome-proliferator-activated receptor gamma (PPARgamma) agonists, rosiglitazone (ros), and 15-deoxy-Delta-(12,14)- prostaglandin J(2) (PGJ2) have been demonstrated to block TNF-alpha-induced lipolysis. Pretreatment of adipocytes with these agents almost totally blocked TNF-alpha-induced ERK activation and reduced lipolysis by greater than 90%. TNF-alpha also stimulated JNK activity, which was not affected by PD98059 or PPARgamma agonist treatment. The expression of perilipin, previously proposed to contribute to the mechanism of lipolysis, is diminished in response to TNF-alpha treatment. Pretreatment of adipocytes with PD98059 or ros significantly blocked the TNF-alpha-induced reduction of perilipin A protein level as determined by Western analysis. These data suggest that activation of the ERK pathway is an early event in the mechanism of TNF-alpha-induced lipolysis.

3T3-L1 Cells↗
PubMed2000

Substrate-dependent lipolysis induced by isoproterenol.

The relationship between isoproterenol-induced lipolysis and the phosphorylation of perilipin and hormone-sensitive lipase (HSL) was examined using cell-free systems consisting of lipid droplets isolated from rat fat cells and HSL, and/or trioleoylglycerol emulsified with gum arabic and HSL. Isoproterenol was found to stimulate lipolysis in the cell-free system with the lipid droplets without an increase in the phosphorylation of either perilipin or HSL. On the other hand, no stimulation of lipolysis was found in the cell-free system containing lipid droplets despite increases in the phosphorylation of perilipin and HSL. In the cell-free system consisting of trioleoylglycerol emulsified with gum arabic and HSL, neither isoproterenol nor increases in the phosphorylation of perilipin and HSL accelerated lipolysis. These results suggest that isoproterenol-induced lipolysis may not be mediated through the phosphorylation of perilipin and HSL, and may rather be dependent on the substrate of HSL.

Adrenergic beta-Agonists↗
PubMed1998

Isolation and chromosomal mapping of the human homolog of perilipin (PLIN), a rat adipose tissue-specific gene, by differential display method.

Using the differential display technique, we isolated a cDNA clone encoding the human homolog of rat perilipin, a unique protein associated with intracellular neutral lipid droplets in adipocytes and steroidogenic cells. The full cDNA contains an open reading frame of 1566 nucleotides encoding 522 amino acids and bears 79% amino acid identity to rat perilipin. Northern blot analysis showed that among 20 human adult tissues examined, human perilipin was expressed specifically in adipose tissues. We determined the chromosomal location of the perilipin gene at 15q26 by means of fluorescence in situ hybridization.

Adipose Tissue↗
PubMed1999

Perilipins, ADRP, and other proteins that associate with intracellular neutral lipid droplets in animal cells.

Although all animal cells package and store neutral lipids in discrete intracellular storage droplets, there is little information on the molecular processes that govern either the deposition or catabolism of the stored lipid components. Studies on adipocytes have uncovered the perilipins and ADRP, related proteins that appear to be intrinsic to the surfaces of intracellular lipid storage droplets. We discuss the properties, distribution, localization, and potential functions of these proteins, as well as those of vimentin and the recently-described 'capsular' proteins, in lipid storage and metabolism.

3T3 Cells↗
PubMed2005

Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population.

Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11-2.46) in Malays and 1.94 (95% CI 1.06-3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28-3.25) and 2.05 (95% CI 1.35-3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10-4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45-3.57) and Indians OR 2.04 (95% CI 1.08-3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans.

Adolescent↗
PubMed2003

Evidence for an important role of perilipin in the regulation of human adipocyte lipolysis.

AIMS/HYPOTHESIS: We investigated the role of the adipocyte-specific protein perilipin for lipolysis in humans. METHODS: Perilipin protein content and lipolysis rates were measured in human subcutaneous fat cells of non-obese (n=10) and obese (n=117) women. Single nucleotide polymorphisms in the perilipin gene were examined in obese subjects. RESULTS: Basal and noradrenaline-induced rates of lipolysis were two to fourfold increased (p<0.01) and perilipin protein content decreased 50% (p=0.005) in adipocytes of the obese women. In subjects matched for body mass index and fat-cell volume, a high rate of lipolysis was associated with a low adipocyte content of perilipin (p=0.01). Adipocyte content of perilipin was inversely correlated with the circulating concentrations of glycerol (r=0.62) and non-esterified fatty acids (n=0.49). A gene polymorphism (rs891460 A/G) in intron 6 was common. In AA subjects basal and noradrenaline induced lipolysis were 50 to 100% times more rapid (p</=0.01) and the adipocyte perilipin content was about 80% reduced (p=0.005) as compared to GG carriers. Intermediate values were found in AG carriers. CONCLUSIONS/INTERPRETATION: Perilipin seems important for the regulation of lipolysis in human fat cells. Obesity and a polymorphism in the perilipin gene associate with decreased protein content of perilipin and increased basal (unstrained) and noradrenaline-induced lipolysis. Low perilipin content also associate with high in vivo lipolytic activity. Perilipin could be a factor behind impaired lipolysis in insulin-resistant conditions.

Adipocytes↗
PubMed2001

The murine perilipin gene: the lipid droplet-associated perilipins derive from tissue-specific, mRNA splice variants and define a gene family of ancient origin.

The Perilipins are a family of intracellular neutral lipid droplet storage proteins that are responsive to acute protein kinase A-mediated, hormonal stimulation. Perilipin (Peri) expression appears to be limited to adipocytes and steroidogenic cells, in which intracellular neutral lipid hydrolysis is regulated by protein kinase A. We have isolated cDNA sets and overlapping genomic fragments of the murine Peri locus and mapped chromosomal location, transcription start sites, polyadenylylation sites, and intron/exon junctions. Data confirm that the Perilipins are encoded by a single-copy gene, with alternative and tissue-specific, mRNA splicing and polyadenylylation yielding four different protein species. The Perilipin proteins have identical approximately 22-kDa amino termini with distinct carboxyl terminal sequences of varying lengths. These genomic and transcriptional maps of murine Perilipin are also essential for evaluating presumptive endogenous and targeted mutations within the locus. The N-terminal identity region of the Perilipins defines a sequence motif, which we term PAT, that is shared with the ADRP and TIP47 proteins; additionally, the PAT domain may represent a novel, conserved pattern for lipid storage droplet (LSD) proteins of vertebrates and invertebrates alike. Comparative genomics suggest the presence of related LSD genes in species as diverse as Drosophila and Dictyostelium.

5' Untranslated Regions↗
PubMed2003

Temporal and spatial assembly of lipid droplet-associated proteins in 3T3-L1 preadipocytes.

This study aimed to investigate the relationship between newly formed lipid droplets and lipid droplet surface proteins, including perilipin, adipose differentiation related protein (ADRP), and p200 kDa protein (p200) in 3T3-L1 preadipocytes, during lipogenesis. Sterol ester was used to induce nascent lipid droplets in 3T3-L1 preadipocytes and the sequence of lipids and lipid droplet surface proteins was studied using a combination of immunohistochemistry and Nile red staining/Oil red O. We demonstrated that, although most growing lipid droplets appeared to have a lipid core surrounded by a fluorescent rim of ADRP, perilipin, and p200, tiny protein aggregates of ADRP, perilipin, or p200 could also be found to occur in the absence of lipid accumulation. In addition, ADRP associated with nascent lipid droplets prior to that of perilipin or p200. We provide evidence that lipid droplet surface proteins, especially ADRP and perilipin, are important in serving as a nucleation center for the assembly of lipid to form nascent lipid droplets.

3T3-L1 Cells↗
PubMed2006

Analysis of interaction partners for perilipin and ADRP on lipid droplets.

Despite the critical roles of intracellular lipid droplets (LDs) in lipid storage and metabolism, little is known about the molecular mechanisms of their functions. Several protein components associated with the surface of LDs have been identified. A major one is perilipin in adipocytes and steroidogenic cells, whereas ADRP in most other cell types. They are loosely grouped as a small protein family sharing a common N-terminal motif, called the PAT domain. Perilipin regulates the breakdown of triacylglycerol in LDs via its phosphorylation. ADRP is characterized as a fatty acid binding protein and involved in lipid uptake and LD formation. For examining the functions of perilipin and ADRP at the molecular level, we performed yeast two-hybrid screening in this study, to find their functional partners. We identified CGI-58, a product of the causal gene of Chanarin-Dorfman syndrome (CDS), as an interactor for both perilipin and ADRP. Specific interaction between CGI-58 and perilipin was confirmed in a GST-pulldown assay and supported by fluorescence microscopic analyses. We further demonstrated that CGI-58 is principally located at the surface of LDs in 3T3-L1 cells, together with perilipin, and its expression is upregulated upon stimulation for adipocyte differentiation. Other than CGI-58, we also identified in yeast two-hybrid screening HSP86 and D52 tumor proteins as binding partners of perilipin, and IRG-47 of ADRP. These factors might be cooperated with perilipin and ADRP, and hence involved in membrane dynamics of LDs as well as the regulation of lipolysis on the surface of LDs.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗
PubMed2006

Aspects of the regulatory mechanisms of PPAR functions: analysis of a bidirectional response element and regulation by sumoylation.

Peroxisome proliferator-activated receptors (PPARs) constitute a subfamily of nuclear receptor superfamily. A wide variety of compounds including hypolipidemic agents, antidiabetic drugs, and long-chain fatty acids are the potential ligands of PPARs. To approach the regulatory mechanisms of PPARs, we studied on two subjects in this work. First, we identified a functional PPAR-binding site in the spacer region between the PEX11alpha and perilipin genes, which are arranged in tandem on the mouse genome. By gene reporter assays and in vivo as well as in vitro binding assays, we show that these genes are regulated tissue-selectively through this common binding site: The PEX11alpha gene is activated by PPARalpha in the liver, whereas the perilipin gene by PPARgamma in the adipose tissue. As the second subject, we found that PPARgamma2 is conjugated with small ubiquitin-related modifier (SUMO) at a specific lysine residue in the amino-terminal region. By site-directed mutagenesis combined with gene reporter assays and sumoylation analyses, we show that sumoylation represses the ligand-independent transactivating function carried by this region, and hence negatively regulates the whole transactivating competence of PPARgamma2. In addition, phosphorylation at a specific site in the amino-terminal region represses the transactivation by PPARgamma2 possibly through enhancing sumoylation.

Adipose Tissue↗
PubMed2006

Perilipin, a potential substitute for adipophilin in triglyceride storage in human macrophages.

Abnormal lipid deposition in human arteries leads to the formation of fatty streaks due to the accumulation of a large number of macrophage derived-foam cells. The formation and catabolism of intracellular lipid droplets is regulated by droplet-associated proteins. Among such proteins, the role of perilipin in human macrophages was unknown. In this study, we first showed that perilipin expression was increased during differentiation of human monocytes to macrophages. Interestingly, cellular perilipin content was unaffected by treatment of cells with OxLDL, AcLDL, VLDL or sterol esters. Moreover, its expression was not dependent on the presence of adipophilin, another lipid droplet-associated protein, since it was not affected by transfection of macrophages with siRNA-adipophilin. Perilipin overexpression in macrophages with an expression vector resulted in significant lipid droplet formation and TG accumulation and this was unaffected by decreasing adipophilin levels using siRNA. Consequently, perilipin, like adipophilin, might play an important role in the conversion of macrophages into foam cells and contribute to lesion formation. Therefore, inhibition of adipophilin might not be sufficient to prevent lesion formation as previously suggested, and perilipin inhibition might be additionally required.

Atherosclerosis↗
PubMed2006

Degradation of perilipin is mediated through ubiquitination-proteasome pathway.

Perilipin protein coats the surface of intracellular lipid droplets and plays fundamental roles in lipid droplet formation and triacylglycerol hydrolysis. Perilipin is transcriptionally regulated through peroxisome proliferator-activated receptor and post-translationally stabilized by stored intracellular neutral lipids. In this study, we show that perilipin protein accumulates in transfected Chinese hamster ovary cells cultured in the presence of fatty acids but in turn is destabilized when lipid precursors for triacylglycerol synthesis are removed from culture serum. Adding fatty acids in the culture medium prevents the degradation of perilipin. Moreover, specific proteasome inhibitors, MG132, lactacystin, and ALLN, block the degradation, whereas inhibitors of other proteases are ineffective. Pulse-chase experiments confirm that perilipin is degraded through proteasome, a process that is inhibited by MG132 or ALLN and blunted by the addition of oleic acid. We have detected the co-immunoprecipitation of perilipin and ubiquitin, thus confirming that perilipin is conjugated to poly-ubiquitin and targeted for proteasomal degradation. Treatment with MG132 increases the expression of perilipin associated with lipid droplets as well as modestly throughout the cytosol. We conclude that the degradation of perilipin is mediated through an ubiquitination-proteasome pathway, which suggests another mode for the post-translational regulation of perilipin.

Animals↗
PubMed2006

Calyculin and okadaic acid promote perilipin phosphorylation and increase lipolysis in primary rat adipocytes.

Lipolysis is primarily regulated by protein kinase A (PKA), which phosphorylates perilipin and hormone-sensitive lipase (HSL), and causes translocation of HSL from cytosol to lipid droplets in adipocytes. Perilipin coats lipid droplet surface and assumes to prevent lipase access to triacylglycerols, thus inhibiting basal lipolysis; phosphorylated perilipin facilitates lipolysis on PKA activation. Here, we induced lipolysis in primary rat adipocytes by inhibiting protein serine/threonine phosphatase with specific inhibitors, okadaic acid and calyculin. The incubation with calyculin promotes incorporation of 32Pi into perilipins, thus, confirming that perilipin is hyperphosphorylated. The lipolysis response to calyculin is gradually accompanied by increased accumulation of phosphorylated perilipin A in a concentration- and time-responsive manner. When perilipin phosphorylation is abrogated by the addition of N-ethylmaleimide, lipolysis ceases. Different from a considerable translocation of HSL upon PKA activation with isoproterenol, calyculin does not alter HSL redistribution in primary or differentiated adipocytes, as confirmed by both immunostaining and immunoblotting. Thus, we suggest that inhibition of the phosphatase by calyculin activates lipolysis via promoting perilipin phosphorylation rather than eliciting HSL translocation in adipocytes. Further, we show that when the endogenous phosphatase is inhibited by calyculin, simultaneous PKA activation with isoproterenol converts most of the perilipin to the hyperphosphorylated species, and induces enhanced lipolysis. Apparently, as PKA phosphorylates perilipin and stimulates lipolysis, the phosphatase acts to dephosphorylate perilipin and attenuate lipolysis. This suggests a two-step strategy governed by a kinase and a phosphatase to modulate the steady state of perilipin phosphorylation and hence the lipolysis response to hormonal stimulation.

Adipocytes↗
PubMed2006

Heat shock protein 70 is translocated to lipid droplets in rat adipocytes upon heat stimulation.

In mammalian cells, lipid storage droplets contain a triacylglycerol and cholesterol ester core surrounded by a phospholipid monolayer into which a number of proteins are imbedded. These proteins are thought to be involved in modulating the formation and metabolic functions of the lipid droplet. In this study, we show that heat stress upregulates several heat shock proteins (Hsps), including Hsp27, Hsp60, Hsp70, Hsp90, and Grp78, in primary and differentiated adipocytes. Immunostaining and immunoblotting data indicate that among the Hsps examined, only Hsp70 is induced to redirect to the lipid droplet surface in heat-stressed adipocytes. The thermal induction of Hsp70 translocation to lipid droplet does not typically happen in a temperature- or time-dependent manner and occurs abruptly at 30-40 min and rapidly achieves a steady state within 60 min after 40 degrees C stress of adipocytes. Though Hsp70 is co-localized with perilipin on the lipid droplets in stressed adipocytes, immunoprecipitation experiments suggest that Hsp70 does not directly interact with perilipin. Alkaline treatments indicate that Hsp70 associates with the droplet surface through non-hydrophobic interactions. We speculate that Hsp70 might noncovalently associate with monolayer microdomains of the lipid droplet in a manner similar to its interaction with lipid bilayer moieties composed of specific fatty acids. As an acute and specific cellular response to the heat stimulation, accumulation of Hsp70 on adipocytes lipid droplets might be involved in stabilizing the droplet monolayer, transferring nascent proteins to the lipid droplets, or chaperoning denatured proteins on the droplet for subsequent refolding.

Adipocytes↗
PubMed2003

Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels.

Transgenic mice overexpressing leptin (LepTg) exhibit substantial reductions in adipose mass. Since the binding of leptin to its receptor activates the sympathetic nervous system, we reasoned that the lean state of the LepTg mice could be caused by chronic lipolysis. Instead, the LepTg mice exhibited a low basal lipolysis state and their lean phenotype was not dependent on the presence of beta3-adrenergic receptors. In their white adipose tissue, protein levels of protein kinase A, hormone-sensitive lipase, and ADRP were not impaired. However, compared to normal mice, perilipin, perilipin mRNA, and cAMP-stimulated PKA activity were significantly attenuated. Overall, we demonstrate that the lean phenotype of the LepTg mice does not result in a chronically elevated lipolytic state, but instead in a low basal lipolysis state characterized by a decrease in perilipin and PKA activity in white fat.

Adipose Tissue↗