TY - JOUR
T1 - Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism
AU - Mishra, Devesh
AU - Richard, Jennifer E.
AU - Maric, Ivana
AU - Porteiro, Begona
AU - Häring, Martin
AU - Kooijman, Sander
AU - Musovic, Saliha
AU - Eerola, Kim
AU - López-Ferreras, Lorena
AU - Peris, Eduard
AU - Grycel, Katarzyna
AU - Shevchouk, Olesya T.
AU - Micallef, Peter
AU - Olofsson, Charlotta S.
AU - Wernstedt Asterholm, Ingrid
AU - Grill, Harvey J.
AU - Nogueiras, Ruben
AU - Skibicka, Karolina P.
N1 - Publisher Copyright:
© 2019 The Author(s)
PY - 2019/3/12
Y1 - 2019/3/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85062358271
UR - https://www.scopus.com/pages/publications/85062358271#tab=citedBy
U2 - 10.1016/j.celrep.2019.02.044
DO - 10.1016/j.celrep.2019.02.044
M3 - Article
C2 - 30865890
AN - SCOPUS:85062358271
SN - 2211-1247
VL - 26
SP - 3011-3026.e5
JO - Cell Reports
JF - Cell Reports
IS - 11
ER -