Proceedings of the National Academy of Sciences - PNAS, 2009-01, Vol.106 (4), p.1105-1110
2009
Details
- Autor(en) / Beteiligte
- Titel
- Retinol saturase promotes adipogenesis and is downregulated in obesity [Erratum: 2009 Mar. 17, v. 106, no. 11, p. 4571.]
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2009-01, Vol.106 (4), p.1105-1110
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2009
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Adipocyte differentiation is controlled by many transcription factors, but few known downstream targets of these factors are necessary for adipogenesis. Here we report that retinol saturase (RetSat), which is an enzyme implicated in the generation of dihydroretinoid metabolites, is induced during adipogenesis and is directly regulated by the transcription factor peroxisome proliferator activated receptor γ (PPARγ). Ablation of RetSat dramatically inhibited adipogenesis but, surprisingly, this block was not overcome by the putative product of RetSat enzymatic activity. On the other hand, ectopic RetSat with an intact, but not a mutated, FAD/NAD dinucleotide-binding motif increased endogenous PPARγ transcriptional activity and promoted adipogenesis. Indeed, RetSat was not required for adipogenesis when cells were provided with exogenous PPARγ ligands. In adipose tissue, RetSat is expressed in adipocytes but is unexpectedly downregulated in obesity, most likely owing to infiltration of macrophages that we demonstrate to repress RetSat expression. Thiazolidinedione treatment reversed low RetSat expression in adipose tissue of obese mice. Thus, RetSat plays an important role in the biology of adipocytes, where it favors normal differentiation, yet is reduced in the obese state. RetSat is thus a novel target for therapeutic intervention in metabolic disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0812065106Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2633572
- Format
- –
- Schlagworte
- 3T3-L1 Cells, Adipocytes, Adipocytes - cytology, Adipocytes - enzymology, Adipogenesis, Adipose tissues, Animals, Base Sequence, Binding Sites, Biological Sciences, Body fat, CCAAT-Enhancer-Binding Protein-beta - metabolism, cell differentiation, Cells, Down-Regulation - genetics, Enzyme Activation, Enzyme Induction, Enzymes, Female, fibroblasts, Gene expression, gene expression regulation, Genes, Humans, Introns - genetics, Ligands, Lipogenesis, Macrophages, Messenger RNA, Metabolic disorders, Mice, Molecular Sequence Data, Nucleotides - metabolism, Obesity, Obesity - enzymology, Obesity - genetics, Obesity - pathology, Oxidoreductases Acting on CH-CH Group Donors - genetics, Oxidoreductases Acting on CH-CH Group Donors - metabolism, peroxisome proliferator activated receptor, PPAR gamma - metabolism, preadipocytes, Response Elements - genetics, Retinoids, retinol saturase, Rodents, transcription (genetics), transcription factors, Transcription, Genetic, Type 2 diabetes mellitus, Vitamin A - analogs & derivatives, Vitamin A - metabolism