*Address all correspondence to:

Ormond A. MacDougald Department of Molecular and Integrative 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@umich.edu

Summary

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 (LXRalpha), 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 LXRalpha 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, LXRalpha 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, LXRalpha increases cholesterol synthesis and release of nonesterified fatty acids. Finally, treatment of mice with an LXRalpha 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 LXRalpha and increase our understanding of adipogenesis.

PMID: 12138207

Supplemental Data

Please acknowledge use of these data in any publications.

1. Genes that define the adipocyte phenotype (from Figure 2)

2. Gene expression profiles during adipogenesis (from Figure 3)

3. Complete microarray data set.