Chemogenetic Excitation of Ventromedial Hypothalamic Steroidogenic Factor 1 (SF1) Neurons Increases Muscle Thermogenesis in Mice.

Allostatic adaptations to a perceived threat are crucial for survival and may tap into mechanisms serving the homeostatic control of energy balance. We previously established that exposure to predator odor (PO) in rats significantly increases skeletal muscle thermogenesis and energy expenditure (EE). Evidence highlights steroidogenic factor 1 (SF1) cells within the central and dorsomedial ventromedial hypothalamus (c/dmVMH) as a modulator of both energy homeostasis and defensive behavior. However, the brain mechanism driving elevated EE and muscle thermogenesis during PO exposure has yet to be elucidated. To assess the ability of SF1 neurons of the c/dmVMH to induce muscle thermogenesis, we used the combined technology of chemogenetics, transgenic mice, temperature transponders, and indirect calorimetry. Here, we evaluate EE and muscle thermogenesis in SF1-Cre mice exposed to PO (ferret odor) compared to transgenic and viral controls. We detected significant increases in muscle temperature, EE, and oxygen consumption following the chemogenetic stimulation of SF1 cells. However, there were no detectable changes in muscle temperature in response to PO in either the presence or absence of chemogenetic stimulation. While the specific role of the VMH SF1 cells in PO-induced thermogenesis remains uncertain, these data establish a supporting role for SF1 neurons in the induction of muscle thermogenesis and EE similar to what is seen after predator threats.

Measuring Skeletal Muscle Thermogenesis in Mice and Rats.

Skeletal muscle thermogenesis provides a potential avenue for better understanding metabolic homeostasis and the mechanisms underlying energy expenditure. Surprisingly little evidence is available to link the neural, myocellular, and molecular mechanisms of thermogenesis directly to measurable changes in muscle temperature. This paper describes a method in which temperature transponders are utilized to retrieve direct measurements of mouse and rat skeletal muscle temperature. Remote transponders are surgically implanted within the muscle of mice and rats, and the animals are given time to recover. Mice and rats must then be repeatedly habituated to the testing environment and procedure. Changes in muscle temperature are measured in response to pharmacological or contextual stimuli in the home cage. Muscle temperature can also be measured during prescribed physical activity (i.e., treadmill walking at a constant speed) to factor out changes in activity as contributors to the changes in muscle temperature induced by these stimuli. This method has been successfully used to elucidate mechanisms underlying muscle thermogenic control at the level of the brain, sympathetic nervous system, and skeletal muscle. Provided are demonstrations of this success using predator odor (PO; ferret odor) as a contextual stimulus and injections of oxytocin (Oxt) as a pharmacological stimulus, where predator odor induces muscle thermogenesis, and Oxt suppresses muscle temperature. Thus, these datasets display the efficacy of this method in detecting rapid changes in muscle temperature.