The Role of Steroidogenic Factor-1 Neurons in Predator Odor-induced Muscle Thermogenesis.

Obesity is one of the most prevalent diseases quietly plaguing this nation. With predictions of its prevalence nearing almost 50% of the adult US population by the end of this decade, it is paramount to identify underlying mechanisms. Characterized by its imbalance of energy intake and energy expenditure, obesity can be countered by amplifying metabolic rate, including inducing thermogenesis. Primarily research has sought to understand adipose tissue thermogenesis, leaving little attention directed toward the brain mechanisms that regulate skeletal muscle thermogenesis. Published evidence from our research program has established that exposure to predator odor (PO) evokes a robust thermogenic response in the skeletal muscle, suggesting that PO works through an unknown brain mechanism causing the thermogenic response. This metabolic response and the stimulation by predator threat each implicate the dorsomedial subregion of the ventromedial hypothalamus (dmVMH), and more specifically, the steroidogenic factor 1 (SF1) cells within it, as a region for further investigation. We hypothesize that SF1 neurons of dmVMH are a key node for predator odor-induced muscle thermogenesis. We use designer receptors exclusively activated by designer drugs (DREADD) delivered using a viral vector to SF1-Cre mice to assess this hypothesis. Utilizing DREADD technology, we stimulated the SF1 cells in the presence of a control odor or PO (ferret odor). Here, we analyze preliminary data looking at the muscle thermogenesis of SF1 Cre mice that have been bilaterally injected with mCherry control vector or an excitatory DREADD vector. Using clozapine-N-oxide (CNO) and manipulation of context (i.e., with or without the presence of PO), we have detected increases in thermogenesis with each PO exposure and CNO activation of SF1 neurons. However, these data provide little to no evidence of DREADD-induced amplification of the PO-induced thermogenesis. Our preliminary data supports the importance of SF1 neurons and their role in regulating PO-induced skeletal muscle thermogenesis.