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

Journal article
Authors Devesh Mishra
Jennifer E. Richard
Ivana Maric
B. Porteiro
M. Haring
S. Kooijman
Musovic Saliha
Kim Eerola
Lorena Lopez-Ferreras
Eduard Peris
Katarzyna Grycel
Olesya Shevchouk
Peter Micallef
Charlotta S Olofsson
Ingrid Wernstedt Asterholm
H. J. Grill
R. Nogueiras
Karolina P Skibicka
Published in Cell Reports
Volume 26
Issue 11
Pages 3011-+
ISSN 2211-1247
Publication year 2019
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Physiology
Pages 3011-+
Language en
Keywords brown adipose-tissue, defective leptin sensitivity, diet-induced, obesity, nucleus contributes, hypothalamic ampk, thyroid-hormones, il-6, production, stress, brain, neurons, Cell Biology
Subject categories Clinical Medicine


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 neuro-anatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (IPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating IPBN neurons. IL-6 microinjection into IPBN 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 IPBN 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 IPBN IL-6. These results indicate that IPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with IPBN IL-6.

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