Inhibition of adipocyte differentiation by RORalpha.
Here we show that gene expression of the nuclear receptor RORalpha is induced during adipogenesis, with RORalpha4 being the most abundantly expressed isoform in human and murine adipose tissue. Over-expression of RORalpha4 in 3T3-L1 cells impairs adipogenesis as shown by the decreased expression of adipogenic markers and lipid accumulation, accompanied by decreased free fatty acid and glucose uptake. By contrast, mouse embryonic fibroblasts from staggerer mice, which carry a mutation in the RORalpha gene, differentiate more efficiently into mature adipocytes compared to wild-type cells, a phenotype which is reversed by ectopic RORalpha4 restoration.
Duez
Hélène
H
Institut Pasteur de Lille, Département d'Athérosclérose, Lille F-59019, France.
Duhem
Christian
C
Laitinen
Saara
S
Patole
Prashant S
PS
Abdelkarim
Mouaadh
M
Bois-Joyeux
Brigitte
B
Danan
Jean-Louis
JL
Staels
Bart
B
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D011994:Recombinant Proteins; D015534:Trans-Activators; D005947:Glucose