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

Devesh Mishra, Jennifer E. Richard, Ivana Maric, Begona Porteiro, Martin Häring, Sander Kooijman, Saliha Musovic, Kim Eerola, Lorena López-Ferreras, Eduard Peris, Katarzyna Grycel, Olesya T. Shevchouk, Peter Micallef, Charlotta S. Olofsson, Ingrid Wernstedt Asterholm, Harvey J. Grill, Ruben Nogueiras, Karolina P. Skibicka

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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.

Original languageEnglish (US)
Pages (from-to)3011-3026.e5
JournalCell Reports
Volume26
Issue number11
DOIs
StatePublished - Mar 12 2019

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mishra, D., Richard, J. E., Maric, I., Porteiro, B., Häring, M., Kooijman, S., Musovic, S., Eerola, K., López-Ferreras, L., Peris, E., Grycel, K., Shevchouk, O. T., Micallef, P., Olofsson, C. S., Wernstedt Asterholm, I., Grill, H. J., Nogueiras, R., & Skibicka, K. P. (2019). Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism. Cell Reports, 26(11), 3011-3026.e5. https://doi.org/10.1016/j.celrep.2019.02.044