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Molecular and Cellular Biology, August 2002, p. 5989-5999, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5989-5999.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Microarray Analyses during Adipogenesis: Understanding the Effects of Wnt Signaling on Adipogenesis and the Roles of Liver X Receptor {alpha} in Adipocyte Metabolism

Sarah E. Ross,1 Robin L. Erickson,1 Isabelle Gerin,1 Paul M. DeRose,2 Laszlo Bajnok,1 Kenneth A. Longo,1 David E. Misek,3 Rork Kuick,3 Samir M. Hanash,3 Kevin B. Atkins,4 Sissel M. Andresen,5 Hilde I. Nebb,5 Lise Madsen,6 Karsten Kristiansen,7 and Ormond A. MacDougald1,2*

Department of Physiology,1 Cell and Molecular Biology Program,2 Department of Pediatrics and Communicative Diseases,3 Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109,4 Institute for Nutrition Research, University of Oslo, Oslo,5 Department of Clinical Biochemistry, University of Bergen, Bergen, Norway,6 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark7

Received 7 January 2002/ Returned for modification 22 February 2002/ Accepted 15 May 2002

Wnt signaling maintains preadipocytes in an undifferentiated state. When Wnt signaling is enforced, 3T3-L1 preadipocytes no longer undergo adipocyte conversion in response to adipogenic medium. Here we used microarray analyses to identify subsets of genes whose expression is aberrant when differentiation is blocked through enforced Wnt signaling. Furthermore, we used the microarray data to identify potentially important adipocyte genes and chose one of these, the liver X receptor {alpha} (LXR{alpha}), for further analyses. Our studies indicate that enforced Wnt signaling blunts the changes in gene expression that correspond to mitotic clonal expansion, suggesting that Wnt signaling inhibits adipogenesis in part through dysregulation of the cell cycle. Experiments designed to uncover the potential role of LXR{alpha} in adipogenesis revealed that this transcription factor, unlike CCAAT/enhancer binding protein {alpha} and peroxisome proliferator-activated receptor gamma, is not adipogenic but rather inhibits adipogenesis if inappropriately expressed and activated. However, LXR{alpha} has several important roles in adipocyte function. Our studies show that this nuclear receptor increases basal glucose uptake and glycogen synthesis in 3T3-L1 adipocytes. In addition, LXR{alpha} increases cholesterol synthesis and release of nonesterified fatty acids. Finally, treatment of mice with an LXR{alpha} agonist results in increased serum levels of glycerol and nonesterified fatty acids, consistent with increased lipolysis within adipose tissue. These findings demonstrate new metabolic roles for LXR{alpha} and increase our understanding of adipogenesis.

* Corresponding author. Mailing address: Department of Physiology, University of Michigan Medical School, 1301 E. Catherine St., Ann Arbor, MI 48109-0622. Phone: (734) 647-4880. Fax: (734) 936-8813. E-mail: macdouga{at}umich.edu.

Molecular and Cellular Biology, August 2002, p. 5989-5999, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5989-5999.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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