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IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure.
Rajbhandari, Prashant; Thomas, Brandon J; Feng, An-Chieh; Hong, Cynthia; Wang, Jiexin; Vergnes, Laurent; Sallam, Tamer; Wang, Bo; Sandhu, Jaspreet; Seldin, Marcus M; Lusis, Aldons J; Fong, Loren G; Katz, Melanie; Lee, Richard; Young, Stephen G; Reue, Karen; Smale, Stephen T; Tontonoz, Peter.
Afiliação
  • Rajbhandari P; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Thomas BJ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Feng AC; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hong C; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang J; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Vergnes L; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sallam T; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wang B; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Sandhu J; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Seldin MM; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Lusis AJ; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Fong LG; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Katz M; Ionis Pharmaceuticals, Carlsbad, CA 92008, USA.
  • Lee R; Ionis Pharmaceuticals, Carlsbad, CA 92008, USA.
  • Young SG; Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Reue K; Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Smale ST; Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tontonoz P; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical
Cell ; 172(1-2): 218-233.e17, 2018 01 11.
Article em En | MEDLINE | ID: mdl-29249357
ABSTRACT
Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the limiters of energy expenditure are largely unknown. Here, we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue. Mechanistic studies define bone marrow cells as the source of the IL-10 signal and adipocytes as the target cell type mediating these effects. IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPß recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-10 / Adipócitos / Termogênese / Montagem e Desmontagem da Cromatina / Metabolismo Energético Tipo de estudo: Health_economic_evaluation / Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Interleucina-10 / Adipócitos / Termogênese / Montagem e Desmontagem da Cromatina / Metabolismo Energético Tipo de estudo: Health_economic_evaluation / Prognostic_studies Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos