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Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism.
Mishra, Devesh; Richard, Jennifer E; Maric, Ivana; Porteiro, Begona; Häring, Martin; Kooijman, Sander; Musovic, Saliha; Eerola, Kim; López-Ferreras, Lorena; Peris, Eduard; Grycel, Katarzyna; Shevchouk, Olesya T; Micallef, Peter; Olofsson, Charlotta S; Wernstedt Asterholm, Ingrid; Grill, Harvey J; Nogueiras, Ruben; Skibicka, Karolina P.
Afiliación
  • Mishra D; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Richard JE; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Maric I; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Porteiro B; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Häring M; Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
  • Kooijman S; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
  • Musovic S; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Eerola K; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • López-Ferreras L; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Peris E; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Grycel K; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Shevchouk OT; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Micallef P; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Olofsson CS; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Wernstedt Asterholm I; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
  • Grill HJ; Lynch Laboratory, Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Nogueiras R; Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
  • Skibicka KP; Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden. Electronic address: karo
Cell Rep ; 26(11): 3011-3026.e5, 2019 03 12.
Article en En | MEDLINE | ID: mdl-30865890
ABSTRACT
Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peso Corporal / Interleucina-6 / Termogénesis / Ingestión de Alimentos / Metabolismo Energético / Núcleos Parabraquiales Límite: Animals Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Suecia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Peso Corporal / Interleucina-6 / Termogénesis / Ingestión de Alimentos / Metabolismo Energético / Núcleos Parabraquiales Límite: Animals Idioma: En Revista: Cell Rep Año: 2019 Tipo del documento: Article País de afiliación: Suecia