Erin Gorrell, Ashley Shemery, Jesse Kowalski, Miranda Bodziony, Nhlalala Mavundza, Amber R. Titus, Mark Yoder, Sarah Mull, Lydia A. Heemstra, Jacob G. Wagner, Megan Gibson, Olivia Carey, Diamond Daniel, Nicholas Harvey, Meredith Zendlo, Megan Rich, Scott Everett, Chaitanya K. Gavini, Tariq I. Almundarij, Diane Lorton, and Colleen M. Novak
Non-shivering thermogenesis can promote negative energy balance and weight loss. In this study, we identify a contextual stimulus that induces rapid and robust thermogenesis in skeletal muscle. Rats exposed to the odor of a natural predator (ferret odor) show elevated skeletal muscle temperatures detectable as quickly as 2 min after exposure, reaching maximum thermogenesis of >1.5 °C at 10-15 min. Mice exhibit a similar thermogenic response to the same odor. Ferret odor induces a significantly larger and qualitatively different response than do novel or aversive odors, fox odor, or moderate restraint stress. Exposure to predator odor increases energy expenditure, and both the thermogenic and energetic effects persist when physical activity levels are controlled. Predator odor-induced muscle thermogenesis is subject to associative learning as exposure to a conditioned stimulus provokes a rise in muscle temperature in the absence of the odor. The ability of predator odor to induce thermogenesis is predominately controlled by sympathetic nervous system activation of β-adrenergic receptors, as unilateral sympathetic lumbar denervation and a peripherally acting β-adrenergic antagonist significantly inhibit predator odor-induced muscle thermogenesis. The potential survival value of predator odor-induced changes in muscle physiology is reflected in an enhanced resistance to running fatigue. Lastly, predator odor-induced muscle thermogenesis imparts a meaningful impact on energy expenditure as daily predator odor exposure significantly enhances weight loss with mild calorie restriction. This evidence signifies contextually provoked, centrally mediated muscle thermogenesis that meaningfully impacts energy balance.