Intact brown adipose tissue thermogenesis is required for restorative sleep responses after sleep loss

• Published in: The European journal of neuroscience 2014-03, Vol.39 (6), p.984-998
• Main Authors: SZENTIRMAI, Éva, KAPAS, Levente
• Format: Article
• Language: English
• Subjects: Adipose tissue (brown); Adipose Tissue, Brown - innervation; Adipose Tissue, Brown - metabolism; Animals; Biological and medical sciences; Body fat; Body Temperature; Brain Waves; Capsaicin; Denervation; EEG; electroencephalogram; Energy expenditure; Food intake; Fundamental and applied biological sciences. Psychology; Gene expression; Ion Channels - genetics; Ion Channels - metabolism; Male; Metabolic disorders; Metabolism; Mice; Mice, Inbred C57BL; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sleep deprivation; Sleep Deprivation - metabolism; Sleep Deprivation - physiopathology; Sleep, REM; Sleep. Vigilance; Thermogenesis; Uncoupling Protein 1; Vertebrates: nervous system and sense organs; Vigilance; Wakefulness
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.12463

Metabolic signals related to feeding and body temperature regulation have profound effects on vigilance. Brown adipose tissue (BAT) is a key effector organ in the regulation of metabolism in several species, including rats and mice. Significant amounts of active BAT are also present throughout adulthood in humans. The metabolic activity of BAT is due to the tissue‐specific presence of the uncoupling protein‐1 (UCP‐1). To test the involvement of BAT thermogenesis in sleep regulation, we investigated the effects of two sleep‐promoting stimuli in UCP‐1‐deficient mice. Sleep deprivation by gentle handling increased UCP‐1 mRNA expression in BAT and elicited rebound increases in non‐rapid‐eye‐movement sleep and rapid‐eye‐movement sleep accompanied by elevated slow‐wave activity of the electroencephalogram. The rebound sleep increases were significantly attenuated, by ~ 35–45%, in UCP‐1‐knockout (KO) mice. Wild‐type (WT) mice with capsaicin‐induced sensory denervation of the interscapular BAT pads showed similar impairments in restorative sleep responses after sleep deprivation, suggesting a role of neuronal sleep‐promoting signaling from the BAT. Exposure of WT mice to 35 °C ambient temperature for 5 days led to increased sleep and body temperature and suppressed feeding and energy expenditure. Sleep increases in the warm environment were significantly suppressed, by ~ 50%, in UCP‐1‐KO animals while their food intake and energy expenditure did not differ from those of the WTs. These results suggest that the metabolic activity of the BAT plays a role in generating a metabolic environment that is permissive for optimal sleep. Impaired BAT function may be a common underlying cause of sleep insufficiency and metabolic disorders. Sleep loss stimulates brown adipose tissue (BAT) thermogenesis. Uncoupling protein‐1 (UCP‐1) knockout mice show fragmented sleep phenotype and attenuated compensatory sleep increases after sleep loss. Sensory denervation of BAT also diminishes sleep rebound after sleep deprivation. The metabolic activity of BAT is required for generating metabolic environment that is permissive for normal sleep. Impaired BAT function may be a common underlying cause of sleep insufficiency and metabolic disorders.