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Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism.

Authors
  • Mishra, Devesh1
  • Richard, Jennifer E1
  • Maric, Ivana1
  • Porteiro, Begona2
  • Häring, Martin3
  • Kooijman, Sander4
  • Musovic, Saliha1
  • Eerola, Kim1
  • López-Ferreras, Lorena1
  • Peris, Eduard1
  • Grycel, Katarzyna1
  • Shevchouk, Olesya T1
  • Micallef, Peter1
  • Olofsson, Charlotta S1
  • Wernstedt Asterholm, Ingrid1
  • Grill, Harvey J5
  • Nogueiras, Ruben2
  • Skibicka, Karolina P6
  • 1 Department of Physiology and Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. , (Sweden)
  • 2 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. , (Spain)
  • 3 Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden. , (Sweden)
  • 4 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. , (Netherlands)
  • 5 Lynch Laboratory, Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 6 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: [email protected] , (Sweden)
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Mar 12, 2019
Volume
26
Issue
11
Identifiers
DOI: 10.1016/j.celrep.2019.02.044
PMID: 30865890
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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