Coordinated Upregulation of Oxidative Pathways and Downregulation of Lipid Biosynthesis Underlie Obesity Resistance in Perilipin Knockout Mice

A Microarray Gene Expression Profile

  1. Fernando Castro-Chavez12,
  2. Vijay K. Yechoor1,
  3. Pradip K. Saha1,
  4. Javier Martinez-Botas1,
  5. Eric C. Wooten1,
  6. Saumya Sharma3,
  7. Peter O’Connell1,
  8. Heinrich Taegtmeyer3 and
  9. Lawrence Chan1
  1. 1Section of Diabetes, Endocrinology and Metabolism, Departments of Molecular & Cellular Biology and Medicine, Baylor College of Medicine, Houston, Texas
  2. 2Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, University Center of Health Sciences, University of Guadalajara, Guadalajara, Mexico
  3. 3Division of Cardiology, University of Texas Houston Medical School, Houston, Texas
  1. Address correspondence and reprint requests to Lawrence Chan, MD, Departments of Medicine and Molecular & Cellular Biology, Section of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. E-mail: lchan{at}bcm.tmc.edu

Abstract

Obesity is a major risk factor for diabetes and heart disease. We previously reported that the inactivation of the gene for perilipin (plin), an adipocyte lipid droplet surface protein, produced lean and obesity-resistant mice. To dissect the underlying mechanisms involved, we used oligonucleotide microarrays to analyze the gene-expression profile of white adipose tissue (WAT), liver, heart, skeletal muscle, and kidney of plin−/− and plin+/+ mice. As compared with wild-type littermates, the WAT of plin−/− mice had 270 and 543 transcripts that were significantly up- or downregulated. There was a coordinated upregulation of genes involved in β-oxidation, the Krebs cycle, and the electron transport chain concomitant with a downregulation of genes involved in lipid biosynthesis. There was also a significant downregulation of the stearoyl CoA desaturase-1 gene, which has been associated with obesity resistance. Thus, in response to the constitutive activation of lipolysis associated with absence of perilipin, WAT activated pathways to rid itself of the products of lipolysis and activated pathways of energy expenditure that contribute to the observed obesity resistance. The biochemical pathways involved in obesity resistance in plin−/− mice identified in this study may represent potential targets for the treatment of obesity.

Footnotes

  • Additional information for this article can be found in a data supplement available at http://diabetes.diabetesjournals.org.

    • Accepted July 30, 2003.
    • Received March 21, 2003.
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