Adipose tissue expression of the lipid droplet-associating proteins S3-12 and perilipin is controlled by peroxisome proliferator-activated receptor-gamma.
In a systematic search for peroxisome proliferator-activated receptor-gamma (PPAR-gamma) target genes, we identified S3-12 and perilipin as novel direct PPAR-gamma target genes. Together with adipophilin and tail-interacting protein of 47 kDa, these genes are lipid droplet-associating proteins with distinct expression pattern but overlapping expression in adipose tissue. The expression of S3-12 and perilipin is tightly correlated to the expression and activation of PPAR-gamma in adipocytes, and promoter characterization revealed that the S3-12 and the perilipin promoters contain three and one evolutionarily conserved PPAR response elements, respectively. 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. Others have shown that perilipin is an essential factor in the hormonal regulation of lipolysis of stored triglycerides within adipose tissue. The direct regulation of perilipin and S3-12 by PPAR-gamma therefore 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.
Dalen
Knut Tomas
KT
Institute for Nutrition Research, University of Oslo, Blindern, N-0316 Oslo, Norway.
Schoonjans
Kristina
K
Ulven
Stine M
SM
Weedon-Fekjaer
Mina Susanne
MS
Bentzen
Trine Gjesti
TG
Koutnikova
Hana
H
Auwerx
Johan
J
Nebb
Hilde I
HI
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins; D002460:Cell Line; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family; D009765:Obesity / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D000070778:Perilipin-1; D000070780:Perilipin-2; D000071229:Perilipin-4; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D008565:Membrane Proteins; D010455:Peptides; D000070778:Perilipin-1; D000070780:Perilipin-2; D000071229:Perilipin-4; D010750:Phosphoproteins; C000602983:Plin2 protein, mouse; C000602984:Plin2 protein, rat; C487119:Plin4 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors