Mishra, DeveshRichard, Jennifer E.Maric, IvanaPorteiro Couto, BegoñaHäring, MartinKooijman, SanderMusovic, SalihaEerola, KimLópez Ferreras, LorenaPeris, EduardGrycel, KatarzynaShevchouk, Olesya T.Micallef, PeterOlofsson, Charlotta S.Wernstedt Asterholm, IngridGrill, Harvey J.Nogueiras Pozo, RubénSkibicka, Karolina P.2020-04-272020-04-272019Mishra et al. (2019). Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism. Cell Reports 26, 3011–3026. doi: 10.1016/j.celrep.2019.02.0442211-1247http://hdl.handle.net/10347/21799Chronic 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-6eng© 2019 The Author(s). Open Access. This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributedhttps://creativecommons.org/licenses/by-nc-nd/4.0/Lateral PBNHindbrainEnergy balanceCold exposureObesityThyroidBrown adipose tissueDiet-induced obesitySex differencesPVNjournal article10.1016/j.celrep.2019.02.044open access