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The generation of immune-induced fever and emotional stress-induced hyperthermia in mice does not involve brown adipose tissue thermogenesis

Journal article
Authors A. Eskilsson
K. Shionoya
Sven Enerbäck
D. Engblom
A. Blomqvist
Published in FASEB Journal
Volume 34
Issue 4
Pages 5863-5876
ISSN 0892-6638
Publication year 2020
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 5863-5876
Language en
Keywords lipopolysaccharide, peroxisome proliferator-activated receptor-gamma, coactivator-1 alpha, uncoupling protein-1, uncoupling protein-3, vasoconstriction, skeletal-muscle, nonshivering thermogenesis, thermoregulatory responses, uncoupling proteins, oxygen-consumption, febrile responses, body-temperature, lipopolysaccharide, receptor, endotoxin, Biochemistry & Molecular Biology, Life Sciences & Biomedicine - Other, Topics, Cell Biology
Subject categories Cell Biology, Biochemistry and Molecular Biology


We examined the role of brown adipose tissue (BAT) for fever and emotional stress-induced hyperthermia. Wild-type and uncoupling protein-1 (UCP-1) knockout mice were injected with lipopolysaccharide intraperitoneally or intravenously, or subjected to cage exchange, and body temperature monitored by telemetry. Both genotypes showed similar febrile responses to immune challenge and both displayed hyperthermia to emotional stress. Neither procedure resulted in the activation of BAT, such as the induction of UCP-1 or peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) mRNA, or reduced BAT weight and triglyceride content. In contrast, in mice injected with a beta (3) agonist, UCP-1 and PGC-1 alpha were strongly induced, and BAT weight and triglyceride content reduced. Both lipopolysaccharide and the beta (3) agonist, and emotional stress, induced UCP-3 mRNA in skeletal muscle. A beta (3) antagonist did not attenuate lipopolysaccharide-induced fever, but augmented body temperature decrease and inhibited BAT activation when mice were exposed to cold. An alpha (1)/alpha (2b) antagonist or a 5HT(1A) agonist, which inhibit vasoconstriction, abolished lipopolysaccharide-induced fever, but had no effect on emotional stress-induced hyperthermia. These findings demonstrate that in mice, UCP-1-mediated BAT thermogenesis does not take part in inflammation-induced fever, which is dependent on peripheral vasoconstriction, nor in stress-induced hyperthermia. However, both phenomena may involve UCP-3-mediated muscle thermogenesis.

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