Coordinated Upregulation of Oxidative Pathways and Downregulation of Lipid Biosynthesis Underlie Obesity Resistance in Perilipin
Knockout Mice
A Microarray Gene Expression Profile
Fernando Castro-Chavez 1 2 ,
Vijay K. Yechoor 1 ,
Pradip K. Saha 1 ,
Javier Martinez-Botas 1 ,
Eric C. Wooten 1 ,
Saumya Sharma 3 ,
Peter O’Connell 1 ,
Heinrich Taegtmeyer 3 and
Lawrence Chan 1
1 Section of Diabetes, Endocrinology and Metabolism, Departments of Molecular & Cellular Biology and Medicine, Baylor College
of Medicine, Houston, Texas
2 Department of Molecular Biology in Medicine, Civil Hospital of Guadalajara, University Center of Health Sciences, University
of Guadalajara, Guadalajara, Mexico
3 Division of Cardiology, University of Texas Houston Medical School, Houston, Texas
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.
Cac, carnitine/acylcarnitine translocase
Cpt, carnitine palmitoyl transferase
Pdk, pyruvate dehydrogenase kinase
PPAR-α, peroxisome proliferator-activated receptor-α
SREBP-1, sterol regulatory element-binding protein-1
WAT, white adipose tissue
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.
DIABETES...

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

10.2337/diabetes.52.11.2666