Microarray analyses during adipogenesis: understanding the effects of Wnt signaling on adipogenesis and the roles of liver X receptor alpha in adipocyte metabolism.
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.
Ross
Sarah E
SE
Department of Physiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Erickson
Robin L
RL
Gerin
Isabelle
I
DeRose
Paul M
PM
Bajnok
Laszlo
L
Longo
Kenneth A
KA
Misek
David E
DE
Kuick
Rork
R
Hanash
Samir M
SM
Atkins
Kevin B
KB
Andresen
Sissel M
SM
Nebb
Hilde I
HI
Madsen
Lise
L
Kristiansen
Karsten
K
MacDougald
Ormond A
OA
D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D005990:Glycerol / Q000097:blood; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D050356:Lipid Metabolism; D000071518:Liver X Receptors; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D057093:Orphan Nuclear Receptors; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D000924:Anticholesteremic Agents; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D005990:Glycerol; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D013449:Sulfonamides; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C000605213:NR1H3 protein, human; C000605214:Nr1h3 protein, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides