TY - JOUR
T1 - Effects of Wnt signaling on brown adipocyte differentiation and metabolism mediated by PGC-1alpha.
AU - Kang, Sona
AU - Bajnok, Laszlo
AU - Longo, Kenneth A
AU - Petersen, Rasmus K
AU - Hansen, Jacob B
AU - Kristiansen, Karsten
AU - MacDougald, Ormond A
N1 - Keywords: Adipocytes; Adipose Tissue, Brown; Animals; CCAAT-Enhancer-Binding Proteins; Carrier Proteins; Cell Differentiation; Fibroblasts; Ion Channels; Membrane Proteins; Mice; Mice, Knockout; Mitochondrial Proteins; PPAR gamma; Proto-Oncogene Proteins; Trans-Activators; Wnt Proteins
PY - 2005
Y1 - 2005
N2 - Activation of canonical Wnt signaling inhibits brown adipogenesis of cultured cells by impeding induction of PPARgamma and C/EBPalpha. Although enforced expression of these adipogenic transcription factors restores lipid accumulation and expression of FABP4 in Wnt-expressing cells, additional expression of PGC-1alpha is required for activation of uncoupling protein 1 (UCP1). Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a beta3-agonist. In differentiated brown adipocytes, activation of Wnt signaling suppresses expression of UCP1 through repression of PGC-1alpha. Consistent with these in vitro observations, UCP1-Wnt10b transgenic mice, which express Wnt10b in interscapular tissue, lack functional brown adipose tissue. While interscapular tissue of UCP1-Wnt10b mice lacks expression of PGC-1alpha and UCP1, the presence of unilocular lipid droplets and expression of white adipocyte genes suggest conversion of brown adipose tissue to white. Reciprocal expression of Wnt10b with UCP1 and PGC-1alpha in interscapular tissue from cold-challenged or genetically obese mice provides further evidence for regulation of brown adipocyte metabolism by Wnt signaling. Taken together, these data suggest that activation of canonical Wnt signaling early in differentiation blocks brown adipogenesis, whereas activating Wnt signaling in mature brown adipocytes stimulates their conversion to white adipocytes.
AB - Activation of canonical Wnt signaling inhibits brown adipogenesis of cultured cells by impeding induction of PPARgamma and C/EBPalpha. Although enforced expression of these adipogenic transcription factors restores lipid accumulation and expression of FABP4 in Wnt-expressing cells, additional expression of PGC-1alpha is required for activation of uncoupling protein 1 (UCP1). Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a beta3-agonist. In differentiated brown adipocytes, activation of Wnt signaling suppresses expression of UCP1 through repression of PGC-1alpha. Consistent with these in vitro observations, UCP1-Wnt10b transgenic mice, which express Wnt10b in interscapular tissue, lack functional brown adipose tissue. While interscapular tissue of UCP1-Wnt10b mice lacks expression of PGC-1alpha and UCP1, the presence of unilocular lipid droplets and expression of white adipocyte genes suggest conversion of brown adipose tissue to white. Reciprocal expression of Wnt10b with UCP1 and PGC-1alpha in interscapular tissue from cold-challenged or genetically obese mice provides further evidence for regulation of brown adipocyte metabolism by Wnt signaling. Taken together, these data suggest that activation of canonical Wnt signaling early in differentiation blocks brown adipogenesis, whereas activating Wnt signaling in mature brown adipocytes stimulates their conversion to white adipocytes.
U2 - 10.1128/MCB.25.4.1272-1282.2005
DO - 10.1128/MCB.25.4.1272-1282.2005
M3 - Journal article
C2 - 15684380
SN - 0270-7306
VL - 25
SP - 1272
EP - 1282
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 4
ER -