Body temperature is highly regulated in mammals. However, thermal biology in smaller mammals (such as mice) is different from that in larger mammals (such as adult humans). For example, when mice are singly housed at room temperature, about half of caloric intake is burned to maintain body temperature (facultative thermogenesis), while humans require little facultative thermogenesis. Upon fasting, mice can reduce their body temperature by >10 C, while humans with extreme starvation lower body temperature by only 0.2 C. We are exploring the use of body temperature as an indicator of the perceived metabolic status of the mouse. For example, what is the effect on body temperature of a genetic manipulation or drug treatment? What genetic manipulations or drug treatments cause dissociation of body temperature from nutritional status? What are the neurotransmitters and neural mechanisms involved? Progress in FY2015 includes the following: We published a study that quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. Environmental temperature was varied from 4 C to 33 C, with continuous monitoring of body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3 null, lipodystrophic). Body temperature depended most on circadian phase and physical activity, but also on environmental temperature. The amounts of energy expenditure due to basal metabolic rate (calculated via a novel method), thermic effect of food, physical activity, and cold-induced thermogenesis were determined as a function of environmental temperature. The measured resting defended body temperature matched that calculated from the energy expenditure using Fouriers law of heat conduction. Mice defended a higher body temperature during physical activity. The cost of the warmer body temperature during the active phase is 4 to 16% of total daily energy expenditure. Parameters measured in diet-induced obese and Brs3 null mice were similar to controls. The high post-mortem heat conductance demonstrates that most insulation in mice is via physiological mechanisms. At 22 C, cold-induced thermogenesis is 120% of basal metabolic rate. The higher body temperature during physical activity is due to a higher set point, not simply increased heat generation during exercise. Most insulation in mice is via physiological mechanisms, with little from fur or fat. Our analysis suggests that the definition of the upper limit of the thermoneutral zone should be re-considered. Measuring body temperature informs interpretation of energy expenditure data and improves the predictiveness and utility of the mouse to model human energy homeostasis.

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4
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2015
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U.S. National Inst Diabetes/Digst/Kidney
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Reitman, Marc L (2018) Of mice and men - environmental temperature, body temperature, and treatment of obesity. FEBS Lett 592:2098-2107
Jain, Shalini; Panyutin, Anna; Liu, Naili et al. (2018) Melanotan II causes hypothermia in mice by activation of mast cells and stimulation of histamine 1 receptors. Am J Physiol Endocrinol Metab 315:E357-E366
Carlin, Jesse Lea; Jain, Shalini; Duroux, Romain et al. (2018) Activation of adenosine A2A or A2B receptors causes hypothermia in mice. Neuropharmacology 139:268-278
Xiao, Cuiying; Piñol, Ramón A; Carlin, Jesse Lea et al. (2017) Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but not GABAergic, neurons is required for regulation of energy metabolism. Mol Metab 6:1540-1550
Carlin, Jesse Lea; Jain, Shalini; Gizewski, Elizabeth et al. (2017) Hypothermia in mouse is caused by adenosine A1 and A3 receptor agonists and AMP via three distinct mechanisms. Neuropharmacology 114:101-113
Carlin, Jesse Lea; Tosh, Dilip K; Xiao, Cuiying et al. (2016) Peripheral Adenosine A3 Receptor Activation Causes Regulated Hypothermia in Mice That Is Dependent on Central Histamine H1 Receptors. J Pharmacol Exp Ther 356:474-82
Lateef, Dalya M; Xiao, Cuiying; Brychta, Robert J et al. (2016) Bombesin-like receptor 3 regulates blood pressure and heart rate via a central sympathetic mechanism. Am J Physiol Heart Circ Physiol 310:H891-8
Abreu-Vieira, Gustavo; Xiao, Cuiying; Gavrilova, Oksana et al. (2015) Integration of body temperature into the analysis of energy expenditure in the mouse. Mol Metab 4:461-70
Lateef, Dalya M; Abreu-Vieira, Gustavo; Xiao, Cuiying et al. (2014) Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3. Am J Physiol Endocrinol Metab 306:E681-7
Goldgof, Margalit; Xiao, Cuiying; Chanturiya, Tatyana et al. (2014) The chemical uncoupler 2,4-dinitrophenol (DNP) protects against diet-induced obesity and improves energy homeostasis in mice at thermoneutrality. J Biol Chem 289:19341-50

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