Back to Search
Start Over
Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation
- Source :
- PLoS ONE, PLoS ONE, Vol 8, Iss 5, p e64605 (2013)
- Publication Year :
- 2013
-
Abstract
- Sterol regulatory element-binding protein-1 (SREBP-1) has been thought to be a critical factor that assists adipogenesis. During adipogenesis SREBP-1 stimulates lipogenic gene expression, and peroxisome proliferator-activated receptor γ (PPARγ) enhances perilipin (plin) gene expression, resulting in generating lipid droplets (LDs) to store triacylglycerol (TAG) in adipocytes. Plin coats adipocyte LDs and protects them from lipolysis. Here we show in white adipose tissue (WAT) of plin-/- mice that nuclear active SREBP-1 and its target gene expression, but not nuclear SREBP-2, significantly decreased on attenuated LD formation. When plin-/- mouse embryonic fibroblasts (MEFs) differentiated into adipocytes, attenuated LDs were formed and nuclear SREBP-1 decreased, but enforced plin expression restored them to their original state. Since LDs are largely derived from the endoplasmic reticulum (ER), alterations in the ER cholesterol content were investigated during adipogenesis of 3T3-L1 cells. The ER cholesterol greatly reduced in differentiated adipocytes. The ER cholesterol level in plin-/- WAT was significantly higher than that of wild-type mice, suggesting that increased LD formation caused a change in ER environment along with a decrease in cholesterol. When GFP-SREBP-1 fusion proteins were exogenously expressed in 3T3-L1 cells, a mutant protein lacking the S1P cleavage site was poorly processed during adipogenesis, providing evidence of the increased canonical pathway for SREBP processing in which SREBP-1 is activated by two cleavage enzymes in the Golgi. Therefore, LD biogenesis may create the ER microenvironment favorable for SREBP-1 activation. We describe the novel interplay between LD formation and SREBP-1 activation through a positive feedback loop.
- Subjects :
- Proteomics
Time Factors
Anatomy and Physiology
Mouse
Gene Expression
Endoplasmic Reticulum
Biochemistry
chemistry.chemical_compound
Mice
Endocrinology
Adipocyte
Lipid droplet
Molecular Cell Biology
Adipocytes
Cells, Cultured
Mice, Knockout
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
food and beverages
Cell Differentiation
Genomics
Animal Models
Lipids
Cell biology
Cholesterol
Adipogenesis
Medicine
lipids (amino acids, peptides, and proteins)
Sterol Regulatory Element Binding Protein 1
Research Article
Perilipin-1
Science
Adipose Tissue, White
Immunoblotting
Biology
Cytoplasmic Granules
Molecular Genetics
Model Organisms
3T3-L1 Cells
Genetics
Animals
Triglycerides
Nutrition
Endoplasmic reticulum
Computational Biology
Fibroblasts
Embryo, Mammalian
Phosphoproteins
Lipid Metabolism
Sterol regulatory element-binding protein
Mice, Inbred C57BL
Metabolism
chemistry
Metabolic Disorders
Perilipin
Carrier Proteins
Developmental Biology
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....03e51649ea0ee0aa234be2ad4712f1bb