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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Mishra D,Richard JE,Maric I,Porteiro B,Häring M,Kooijman S,Musovic S,Eerola K,López-Ferreras L,Peris E,Grycel K,Shevchouk OT,Micallef P,Olofsson CS,Wernstedt Asterholm I,Grill HJ,Nogueiras R,Skibicka KPdoi
10.1016/j.celrep.2019.02.044subject
Has Abstractpub_date
2019-03-12 00:00:00pages
3011-3026.e5issue
11issn
2211-1247pii
S2211-1247(19)30215-3journal_volume
26pub_type
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