Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor alpha in adipocyte metabolism

TY - JOUR

T1 - Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor alpha in adipocyte metabolism

AU - Ross, Sarah E

AU - Erickson, Robin L

AU - Gerin, Isabelle

AU - DeRose, Paul M

AU - Bajnok, Laszlo

AU - Longo, Kenneth A

AU - Misek, David E

AU - Kuick, Rork

AU - Hanash, Samir M

AU - Atkins, Kevin B

AU - Andresen, Sissel M

AU - Nebb, Hilde I

AU - Madsen, Lise

AU - Kristiansen, Karsten

AU - MacDougald, Ormond A

N1 - Keywords: Adipocytes; Adipose Tissue; Animals; Anticholesteremic Agents; Cell Differentiation; Cells, Cultured; DNA-Binding Proteins; Fatty Acids, Nonesterified; Female; Gene Expression Profiling; Glycerol; Humans; Ligands; Lipid Metabolism; Mice; Mice, Inbred C57BL; Oligonucleotide Array Sequence Analysis; Phenotype; Proto-Oncogene Proteins; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Receptors, Thyroid Hormone; Signal Transduction; Sulfonamides; Wnt Proteins; Zebrafish Proteins

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12138207

SN - 0270-7306

VL - 22

SP - 5989

EP - 5999

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 16

ER -