Chronic REM-sleep deprivation of rats elevates metabolic rate and increases UCP1 gene expression in brown adipose tissue

• Published in: American journal of physiology: endocrinology and metabolism Vol. 289; no. 1; pp. E68 - E74
• Main Authors: Koban, Michael, Swinson, Kevin L
• Format: Journal Article
• Language: English
• Published: United States 01.07.2005
• Subjects: Adipose Tissue, Brown - metabolism; Animals; Carrier Proteins - metabolism; Energy Metabolism; Gene Expression Regulation; Hyperphagia - etiology; Hyperphagia - metabolism; Ion Channels; Membrane Proteins - metabolism; Men; Mitochondrial Proteins; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Sleep Deprivation - complications; Sleep Deprivation - metabolism; Thermogenesis; Uncoupling Protein 1
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00543.2004

Laboratory of Physiology, Department of Biology, Morgan State University, Baltimore, Maryland Submitted 11 November 2004 ; accepted in final form 14 February 2005 A cluster of unique pathologies progressively develops during chronic total- or rapid eye movement-sleep deprivation (REM-SD) of rats. Two prominent and readily observed symptoms are hyperphagia and decline in body weight. For body weight to be lost despite a severalfold increase in food consumption suggests that SD elevates metabolism as the subject enters a state of negative energy balance. To test the hypothesis that mediation of this hypermetabolism involves increased gene expression of uncoupling protein-1 (UCP1), which dissipates the thermodynamic energy of the mitochondrial proton-motive force as heat instead of ATP formation in brown adipose tissue (BAT), we 1 ) established the time course and magnitude of change in metabolism by measuring oxygen consumption, 2 ) estimated change in UCP1 gene expression in BAT by RT-PCR and Western blot, and 3 ) assayed serum leptin because of its role in regulating energy balance and food intake. REM-SD of male Sprague-Dawley rats was enforced for 20 days with the platform (flowerpot) method, wherein muscle atonia during REM sleep causes contact with surrounding water and awakens it. By day 20 , rats more than doubled food consumption while losing 11% of body weight; metabolism rose to 166% of baseline with substantial increases in UCP1 mRNA and immunoreactive UCP1 over controls; serum leptin decreased and remained suppressed. The decline in leptin is consistent with the hyperphagic response, and we conclude that one of the mediators of elevated metabolism during prolonged REM-SD is increased gene expression of UCP1 in BAT. rapid eye movement; oxygen consumption; uncoupling protein-1 Address for reprint requests and other correspondence: M. Koban, Laboratory of Physiology, Richard N. Dixon Science Research Bldg., Dept. of Biology, Morgan State University, 1700 E. Cold Spring Ln., Baltimore, MD 21251 (e-mail: mkoban{at}aol.com )