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  • 1
    Publication Date: 2008-07-25
    Description: Inadequate physical activity is linked to many chronic diseases. But the mechanisms that tie muscle activity to health are unclear. The transcriptional coactivator PGC1alpha has recently been shown to regulate several exercise-associated aspects of muscle function. We propose that this protein controls muscle plasticity, suppresses a broad inflammatory response and mediates the beneficial effects of exercise.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587487/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2587487/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Handschin, Christoph -- Spiegelman, Bruce M -- R01 DK054477/DK/NIDDK NIH HHS/ -- R01 DK054477-09A1/DK/NIDDK NIH HHS/ -- England -- Nature. 2008 Jul 24;454(7203):463-9. doi: 10.1038/nature07206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, CH-8057 Zurich, Switzerland. christoph.handschin@access.uzh.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18650917" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chronic Disease ; Exercise/*physiology ; Humans ; Inflammation/genetics/*metabolism ; Muscle, Skeletal/metabolism/physiology ; Obesity/genetics/immunology/physiopathology ; Transcription Factors/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2009-07-31
    Description: Brown adipose cells are specialized to dissipate chemical energy in the form of heat, as a physiological defence against cold and obesity. PRDM16 (PR domain containing 16) is a 140 kDa zinc finger protein that robustly induces brown fat determination and differentiation. Recent data suggests that brown fat cells arise in vivo from a Myf5-positive, myoblastic lineage by the action of PRDM16 (ref. 3); however, the molecular mechanisms responsible for this developmental switch is unclear. Here we show that PRDM16 forms a transcriptional complex with the active form of C/EBP-beta (also known as LAP), acting as a critical molecular unit that controls the cell fate switch from myoblastic precursors to brown fat cells. Forced expression of PRDM16 and C/EBP-beta is sufficient to induce a fully functional brown fat program in naive fibroblastic cells, including skin fibroblasts from mouse and man. Transplantation of fibroblasts expressing these two factors into mice gives rise to an ectopic fat pad with the morphological and biochemical characteristics of brown fat. Like endogenous brown fat, this synthetic brown fat tissue acts as a sink for glucose uptake, as determined by positron emission tomography with fluorodeoxyglucose. These data indicate that the PRDM16-C/EBP-beta complex initiates brown fat formation from myoblastic precursors, and may provide opportunities for the development of new therapeutics for obesity and type-2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754867/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754867/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kajimura, Shingo -- Seale, Patrick -- Kubota, Kazuishi -- Lunsford, Elaine -- Frangioni, John V -- Gygi, Steven P -- Spiegelman, Bruce M -- DK081605/DK/NIDDK NIH HHS/ -- DK31405/DK/NIDDK NIH HHS/ -- GM67945/GM/NIGMS NIH HHS/ -- HG3456/HG/NHGRI NIH HHS/ -- K99 DK087853/DK/NIDDK NIH HHS/ -- R37 DK031405/DK/NIDDK NIH HHS/ -- R37 DK031405-28/DK/NIDDK NIH HHS/ -- S10-RR-023010/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1154-8. doi: 10.1038/nature08262. Epub 2009 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641492" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, Brown/*cytology/*metabolism ; Animals ; CCAAT-Enhancer-Binding Protein-beta/genetics/*metabolism ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Choristoma/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Fibroblasts/cytology/metabolism ; Glucose/metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Multiprotein Complexes ; Myoblasts/*cytology/*metabolism ; Skin/cytology ; Transcription Factors/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-08-16
    Description: Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPARgamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPARgamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Jeong-Ho -- Hwang, Eun Sook -- McManus, Michael T -- Amsterdam, Adam -- Tian, Yu -- Kalmukova, Ralitsa -- Mueller, Elisabetta -- Benjamin, Thomas -- Spiegelman, Bruce M -- Sharp, Phillip A -- Hopkins, Nancy -- Yaffe, Michael B -- CA042063/CA/NCI NIH HHS/ -- GM60594/GM/NIGMS NIH HHS/ -- GM68762/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Aug 12;309(5737):1074-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16099986" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*cytology ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/pharmacology ; Cell Differentiation ; Cell Line ; Core Binding Factor Alpha 1 Subunit ; Gene Expression Regulation, Developmental ; Humans ; Mesenchymal Stromal Cells/*cytology/physiology ; Mice ; Neoplasm Proteins/metabolism ; Oligonucleotides, Antisense ; Osteoblasts/*cytology ; Osteocalcin/genetics ; Osteogenesis ; PPAR gamma/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Proteins/chemistry/genetics/*physiology ; RNA, Small Interfering ; Transcription Factors/chemistry/genetics/metabolism/*physiology ; Transcriptional Activation ; Transfection ; Transforming Growth Factor beta/pharmacology ; Zebrafish ; Zebrafish Proteins/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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