Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1
| Autor: | Michinori Kohara, Anne-Claude Gingras, Nahum Sonenberg, Zhidan Wu, Asao Katsume, Kyoko Tsukiyama-Kohara, Mounib Elchebly, Mary-Ellen Harper, Bruce M. Spiegelman, Alan Cheng, Christine T. DeMaria, Michel L. Tremblay, Francis Poulin |
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| Rok vydání: | 2001 |
| Předmět: |
Male
medicine.medical_specialty FGF21 Adipose tissue macrophages Adipose tissue Cell Cycle Proteins White adipose tissue Biology General Biochemistry Genetics and Molecular Biology Ion Channels Mitochondrial Proteins Mice Peptide Initiation Factors Internal medicine medicine Animals RNA Messenger Eukaryotic Initiation Factors Phosphorylation Uncoupling Protein 1 Adaptor Proteins Signal Transducing PRDM16 Mice Knockout Mice Inbred BALB C EIF4E Membrane Proteins General Medicine Phosphoproteins Thermogenin Hypoglycemia Cell biology Repressor Proteins Endocrinology Eukaryotic Initiation Factor-4E Adipose Tissue Gene Expression Regulation Adipogenesis Protein Biosynthesis Gene Targeting Basal Metabolism Carrier Proteins Transcription Factors |
| Zdroj: | Nature medicine. 7(10) |
| ISSN: | 1078-8956 |
| Popis: | All nuclear-encoded mRNAs contain a 5' cap structure (m7GpppN, where N is any nucleotide), which is recognized by the eukaryotic translation initiation factor 4E (eIF4E) subunit of the eIF4F complex. The eIF4E-binding proteins constitute a family of three polypeptides that reversibly repress cap-dependent translation by binding to eIF4E, thus preventing the formation of the eIF4F complex. We investigated the biological function of 4E-BP1 by disrupting its gene (Eif4ebp1) in the mouse. Eif4ebp1-/- mice manifest markedly smaller white fat pads than wild-type animals, and knockout males display an increase in metabolic rate. The males' white adipose tissue contains cells that exhibit the distinctive multilocular appearance of brown adipocytes, and expresses the uncoupling protein 1 (UCP1), a specific marker of brown fat. Consistent with these observations, translation of the peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC1), a transcriptional co-activator implicated in mitochondrial biogenesis and adaptive thermogenesis, is increased in white adipose tissue of Eif4ebp1-/- mice. These findings demonstrate that 4E-BP1 is a novel regulator of adipogenesis and metabolism in mammals. |
| Databáze: | OpenAIRE |
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