Adipose Tissue Expression of the Lipid Droplet–Associating Proteins S3-12 and Perilipin Is Controlled by Peroxisome Proliferator–Activated Receptor-γ

  1. Knut Tomas Dalen1,
  2. Kristina Schoonjans2,
  3. Stine M. Ulven1,
  4. Mina Susanne Weedon-Fekjaer1,
  5. Trine Gjesti Bentzen1,
  6. Hana Koutnikova2,
  7. Johan Auwerx2 and
  8. Hilde I. Nebb1
  1. 1Institute for Nutrition Research, University of Oslo, Oslo, Norway
  2. 2Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS, INSERM, Illkirch, France
  1. Address correspondencereprint requests to Hilde Irene Nebb, Institute for Nutrition Research, University of Oslo, P.O. Box 1046 Blindern, N-0316 Oslo, Norway. E-mail: h.i.nebb{at}basalmed.uio.no

Abstract

In a systematic search for peroxisome proliferator–activated receptor-γ (PPAR-γ) target genes, we identified S3-12 and perilipin as novel direct PPAR-γ 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-γ 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-γ therefore is likely to be an important mediator of the in vivo effects of prolonged treatment with PPAR-γ activators: insulin sensitization, fatty acid trapping in adipose tissue, reduced basal adipose lipolysis, and weight gain.

Footnotes

  • J.A. is on the scientific advisory board of CareX SA, a biotechnology company with a focus on developing therapies for syndrome X.

    Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    • Accepted January 23, 2004.
    • Received November 3, 2003.
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