OXPAT/PAT-1 Is a PPAR-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization

@article{Wolins2006OXPATPAT1IA,
  title={OXPAT/PAT-1 Is a PPAR-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization},
  author={Nathan Edward Wolins and Benjamin K Quaynor and James R. Skinner and Anatoly Tzekov and Michelle A. Croce and Matthew C. Gropler and Vijayalakshmi Varma and Aiwei Yao-Borengasser and Neda Rasouli and Philip A. Kern and Brian N. Finck and Perry E Bickel},
  journal={Diabetes},
  year={2006},
  volume={55},
  pages={3418 - 3428}
}
Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as “OXPAT.” Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes… Expand

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Interventional Clinical Trial
Subjects with impaired glucose tolerance will be randomized to receive pioglitazone or metformin for 10 weeks. Measurements of insulin sensitivity, body composition, glucose… Expand
ConditionsDiabetes, Glucose Metabolism Disorders
InterventionDrug, Procedure, Radiation
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References

SHOWING 1-10 OF 61 REFERENCES
PPARα activators and fasting induce the expression of adipose differentiation-related protein in livers⃞
TLDR
It is demonstrated that ADFP is transcriptionally regulated by peroxisome proliferator-activated receptor α (PPARα) in mouse liver and rat and human hepatoma cells through a highly conserved direct repeat-1(DR-1) element and suggested that AD FP is primarily a fasting-induced protein in liver that coats the newly synthesized triacylglycerol-containing LDs formed during fasting. Expand
The Central Role of Perilipin A in Lipid Metabolism and Adipocyte Lipolysis
TLDR
This review will focus on adipocyte lipolysis with emphasis on hormone signal transduction, lipolytic enzymes, the lipid storage droplet, and fatty acid release from the adipocyte. Expand
Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein
TLDR
The reduction of TG in the cytosol with concomitant accumulation ofTG in the microsome of Adfp−/− cells suggests that ADFP may facilitate the formation of new LDs, which are thought to form from the outer leaflet of the microsomal membrane. Expand
Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma.
TLDR
The direct regulation of perilipin and S3-12 by PPAR-gamma is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR -gamma activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain. Expand
MLDP, a Novel PAT Family Protein Localized to Lipid Droplets and Enriched in the Heart, Is Regulated by Peroxisome Proliferator-activated Receptor α*
TLDR
Results indicate that MLDP is a bona fide new PAT family member localized in LDs, and its expression depends on the physiological conditions and the action of PPARα. Expand
Proteomic Analysis of Proteins Associated with Lipid Droplets of Basal and Lipolytically Stimulated 3T3-L1 Adipocytes*
TLDR
Adipocytes contain specific structural proteins as well as lipid metabolic enzymes; the structural reorganization of lipid droplets in response to the hormonal stimulation of lipolysis is accompanied by increases in the relative mass of several proteins and the recruitment of additional proteins. Expand
A critical role for the peroxisome proliferator-activated receptor alpha (PPARalpha) in the cellular fasting response: the PPARalpha-null mouse as a model of fatty acid oxidation disorders.
TLDR
A critical role for PPAR alpha is defined in a transcriptional regulatory response to fasting and the PPARalpha-/- mouse is identified as a potentially useful murine model of inborn and acquired abnormalities of human fatty acid utilization. Expand
ADRP stimulates lipid accumulation and lipid droplet formation in murine fibroblasts.
TLDR
In conclusion, ADRP stimulated lipid accumulation and lipid droplet formation without induction of other adipocyte-specific genes or other lipogenic genes in murine fibroblasts, and the detailed molecular mechanisms of ADRP on lipid accumulation remain to be elucidated. Expand
Post-translational Regulation of Adipose Differentiation-related Protein by the Ubiquitin/Proteasome Pathway*
TLDR
It is shown 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. Expand
Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro.
TLDR
The direct energy-dissipating effects of the cAMP or PPARgamma pathway pushes the white adipocyte down the oxidative continuum and could be significant tools to treat obesity and to improve insulin resistance in type 2 diabetic patients. Expand
...
1
2
3
4
5
...