Disease relevance of Adfp

• The gene encoding mouse ADRP has been isolated and characterized from four overlapping lambda phage clones [1].
• Protection against fatty liver but normal adipogenesis in mice lacking adipose differentiation-related protein [2].
• Immunocytochemical examination revealed that ADRP localizes to neutral lipid storage droplets in cultured murine 3T3-L1 adipocytes, murine MA-10 Leydig cells, Chinese hamster ovary (CHO) fibroblasts, and human HepG2 hepatoma cells; the association of ADRP with lipid droplets was confirmed by subcellular fractionation of MA-10 Leydig cells [3].
• Adipose differentiation related protein: expression, purification of recombinant protein in Escherichia coli and characterization of its fatty acid binding properties [4].
• These results provide evidence that the loss-of-function phenotype seen in C214S transgenic mice shows a disease progression that correlates with ADRP patients carrying the same mutation, indicating that the C214S mutation on one allele of P/rds results in haploinsufficiency [5].

High impact information on Adfp

• They contain hydrophobic substances, a set of structural proteins such as perilipin or adipose differentiation-related protein, enzymes implicated in lipid metabolism, and proteins that participate in signaling and membrane trafficking [6].
• These structures form autonomous all-trans-retinyl ester-rich intracellular compartments distinct from other organelles and colocalize with adipose differentiation-related protein [7].
• These proteins exhibit a significant sequence relationship (approximately 65% similarity through 105 aa) with only one other known protein, the adipocyte differentiation-related protein (ADRP) [8].
• Dvl, the mouse homolog of the putative Drosophila dishevelled gene, and Adfp, encoding an adipocyte differentiation-related protein, were found to map to chromosome 4 [9].
• The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled [2].

Chemical compound and disease context of Adfp

• In the present paper, the murine ADRP has been expressed as a recombinant histidine-tagged protein in Escherichia coli, and purified from expressing cultures in order to examine its biochemical properties [4].

Biological context of Adfp

• The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo [2].
• Furthermore, we identified CGI-58 as a binding partner of ADRP, another PAT domain protein expressed ubiquitously, by yeast two-hybrid assay [10].
• Adipose differentiation-related protein and regulators of lipid homeostasis identified by gene expression profiling in the murine db/db diabetic kidney [11].
• The structural and functional roles of adipophilin and perilipin in gestation and labor remain to be determined [12].
• 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 [13].

Anatomical context of Adfp

• Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp-/- cells suggests that ADFP may facilitate the formation of new LDs [2].
• ADRP, proposed to regulate fatty acid mobilization and lipid droplet formation, is linked to lipid accumulation in foam cells of human atherosclerotic lesions [14].
• In this report, we show that ADRP protein accumulates in Chinese hamster ovary fibroblastic cells cultured in the presence of oleic acid but is destabilized when fatty acid sources are removed from culture serum [14].
• This finding was confirmed at the protein level by Western blotting, and immunohistochemistry localized ADRP diffusely to tubular epithelium throughout the cortex [11].
• ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts [15].

Associations of Adfp with chemical compounds

• Overexpressed GFP-ADRP were mainly located at the surface of lipid droplets and appeared to be "ring-shaped." Triacylglycerol content was also significantly (P < 0.001) increased in GFP-ADRP-overexpressed cells compared with control cells [15].
• Expression and localization of adipophilin and perilipin in human fetal membranes: association with lipid bodies and enzymes involved in prostaglandin synthesis [12].
• The present study showed that the GDP-bound ARF1 induces dissociation of ADRP from the LD surface, and that LD is a target of BFA action [16].
• Displacement studies showed differential binding affinity of ADRP for cholesterol and fatty acids [17].
• The oleate uptake measured at 4 degrees C was only 10% that at 37 degrees C. ADRP also stimulated uptake of palmitate and arachidonate but had no effect on uptake of medium chain fatty acid such as octanoic acid and glucose [18].

Regulatory relationships of Adfp

• Our recent report suggests that the association of adipose differentiation-related protein (ADRP) to LDs is regulated by an ADP-ribosylation factor 1 (Arf1)-dependent mechanism [19].
• These data suggested that SCP-2 and ADRP play a significant role in regulating fatty acid and cholesterol targeting to lipid droplets as well as in determining their lipid and protein components [17].

Other interactions of Adfp

• The presence of significant sequence similarities within an approximately 100 amino acid region of the N-terminal portions of ADPH and related LSD binding proteins, perilipin and TIP47, has implicated this region, known as the "PAT" domain, in LSD targeting [20].
• ADRP has been mapped to chromosome 4, specifically between the b and Ifa loci [1].
• Post-translational regulation of adipose differentiation-related protein by the ubiquitin/proteasome pathway [14].
• Adipose differentiation-related protein (ADRP) is a novel 50-kDa membrane-associated protein whose message levels are induced rapidly and maximally after triggering adipocyte differentiation [1].
• We furthermore demonstrate that the expression of S3-12 and perilipin is reduced in obese compared with lean Zucker rats, whereas the expression of adipophilin is increased [21].

Analytical, diagnostic and therapeutic context of Adfp

• Furthermore, co-existence of PLD1, Arf1, and ADRP was observed in the LD-enriched subcellular fractions obtained from oleic acid-treated NIH3T3 cells by Western blot analysis [19].
• The interaction of ADRP and ARF1 was verified by GST pull-down and co-immunoprecipitation experiments [16].
• Sequence analysis of this cDNA indicates that it encodes a protein of the 425 amino acids [tentatively named adipose differentiation-related protein (ADRP)] that does not have any similarity with sequences contained in the GenBank DNA and Protein Identification Resource protein data bases [22].
• These results correspond with an increase in the lipid droplet protein, ADRP, and the data demonstrate that ADRP functions to coat lipid droplets in hepatocytes as observed by confocal microscopy [23].
• Immunofluorescence studies also showed that ADRP became detached from the surface of lipid droplets after magnolol treatment [24].

References