Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes.
Retinoid X receptor alpha (RXRalpha) is involved in multiple signaling pathways, as a heterodimeric partner of several nuclear receptors. To investigate its function in energy homeostasis, we have selectively ablated the RXRalpha gene in adipocytes of 4-week-old transgenic mice by using the tamoxifen-inducible Cre-ERT2 recombination system. Mice lacking RXRalpha in adipocytes were resistant to dietary and chemically induced obesity and impaired in fasting-induced lipolysis. Our results also indicate that RXRalpha is involved in adipocyte differentiation. Thus, our data demonstrate the feasibility of adipocyte-selective temporally controlled gene engineering and reveal a central role of RXRalpha in adipogenesis, probably as a heterodimeric partner for peroxisome proliferator-activated receptor gamma.
Imai
T
T
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, Collège de France, BP 163, 67404 Illkirch Cedex, France.
Jiang
M
M
Chambon
P
P
Metzger
D
D
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D019281:Dimerization; D004790:Enzyme Induction / Q000187:drug effects; D005215:Fasting; D006651:Histocytochemistry; D007035:Hypothermia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D012970:Sodium Glutamate / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014764:Viral Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases; D012970:Sodium Glutamate