Expression of human (beta)3-adrenergic receptor induces adipocyte-like features in CHO/K1 fibroblasts.
It is reported here that CHO/K1 cells stably transfected with the human (beta)3 AR gene (CHO/K1-(beta)3), grown in the presence of differentiation-stimulating agents accumulate triglycerides. This lipid formation is mediated through the (beta)3 AR, since non-transfected CHO/K1 cells, or cells expressing the human (beta)2 AR, accumulate no significant amount of lipids when grown in supplemented medium. Moreover, lipid production can be inhibited significantly by the (beta) AR antagonist bupranolol. CHO/K1 cells expressing the W64R polymorphism (Trp to Arg polymorphism at position 64 of the human (beta)3 AR), which has been associated with morbid obesity, show increased lipid accumulation as compared to CHO/K1 cells expressing the wild-type (beta)3 AR. Semi-quantitative RT-PCR experiments reveal that a major gene regulating adipocyte differentiation, peroxisome-proliferator-activated-receptor (gamma) (PPAR(gamma)), is expressed in CHO/K1 cells. Concomitantly with the formation of lipid droplets, the expression of PPAR(gamma) mRNA is increased in CHO/K1-(beta)3 cells, but not in non-transfected CHO/K1 cells. We furthermore detected constitutive expression of another adipocyte-associated protein: hormone sensitive lipase, while leptin or uncoupling protein-1 transcripts were not expressed. These data suggest that the frequently used CHO/K1 fibroblasts display several preadipocyte-like features, and that the sole expression of the (beta)3 AR modifies the expression of PPAR(gamma) mRNA in these cells, and induces lipid formation under certain culture conditions.
Gros
J
J
Laboratoire d'Immunopharmacologie Moléculaire, CNRS-UPR415 and Université Paris VII, Institut Cochin de Génétique Moléculaire, Paris, France.
Gerhardt
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Strosberg
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D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D016466:CHO Cells / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D004396:Coloring Agents / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D012333:RNA, Messenger / Q000032:analysis; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*
D001391:Azo Compounds; D004396:Coloring Agents; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C011049:oil red O