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Dynamics of lipid droplet-associated proteins during hormonally stimulated lipolysis in engineered adipocytes: stabilization and lipid droplet binding of adipocyte differentiation-related protein/adipophilin.
- Source :
-
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2006 Feb; Vol. 20 (2), pp. 459-66. Date of Electronic Publication: 2005 Oct 20. - Publication Year :
- 2006
-
Abstract
- In mature adipocytes, triglyceride is stored within lipid droplets, which are coated with the protein perilipin, which functions to regulate lipolysis by controlling lipase access to the droplet in a hormone-regulatable fashion. Adipocyte differentiation-related protein (ADRP) is a widely expressed lipid droplet binding protein that is coexpressed with perilipin in differentiating fat cells but is minimally present in fully differentiated cultured adipocytes. We find that fibroblasts ectopically expressing C/EBPalpha (NIH-C/EBPalpha cells) differentiate into mature adipocytes that simultaneously express perilipin and ADRP. In response to isoproterenol, perilipin is hyperphosphorylated, lipolysis is enhanced, and subsequently, ADRP expression increases coincident with it surrounding intracellular lipid droplets. In the absence of lipolytic stimulation, inhibition of proteasomal activity with MG-132 increased ADRP levels to those of cells treated with 10 mum isoproterenol, but ADRP does not surround the lipid droplet in the absence of lipolytic stimulation. We overexpressed a perilipin A construct in NIH-C/EBPalpha cells where the six serine residues known to be phosphorylated by protein kinase A were changed to alanine (Peri A Delta1-6). These cells show no increase in ADRP expression in response to isoproterenol. We propose that ADRP can replace perilipin on existing lipid droplets or those newly formed as a result of fatty acid reesterification, under dynamic conditions of hormonally stimulated lipolysis, thus preserving lipid droplet morphology/structure.
- Subjects :
- Adipocytes drug effects
Animals
CCAAT-Enhancer-Binding Protein-alpha genetics
CCAAT-Enhancer-Binding Protein-alpha metabolism
Carrier Proteins
Cysteine Proteinase Inhibitors pharmacology
Hormones pharmacology
Isoproterenol pharmacology
Leupeptins pharmacology
Lipid Metabolism
Mice
NIH 3T3 Cells
Perilipin-1
Perilipin-2
Phosphoproteins genetics
Phosphorylation
Proteasome Inhibitors
Adipocytes metabolism
Lipolysis
Membrane Proteins metabolism
Peptides metabolism
Phosphoproteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0888-8809
- Volume :
- 20
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular endocrinology (Baltimore, Md.)
- Publication Type :
- Academic Journal
- Accession number :
- 16239256
- Full Text :
- https://doi.org/10.1210/me.2005-0323