Dr. Kotz's team uses neuromodulation techniques to understand the role of the neurohormone orexin in energy balance. Her laboratory first developed the idea that orexin drives spontaneous physical activity (SPA) and non-exercise activity thermogenesis (NEAT); that it interacts with other neurotransmitters and brain sites in a network fashion; and that it has relevance to obesity: higher orexin signaling is associated with greater SPA and NEAT, the lean state and obesity resistance. Recently they have shown that orexin stimulation - either by direct receptor stimulation with orexin A injections in rats, or by DREADD [Designer Receptors Exclusively Activated by Designer Drugs] stimulation of orexin neurons in mice, prevents diet-induced adiposity and weight gain. This, coupled with our use of optogenetics to understand effects of acute simulation and inhibition of orexin neurons, and the recent development of the CAV2-Cre virus, which transfers Cre recombinase retrogradely between neurons, allows us to begin the study of orexin thermogenic pathways relevant to obesity.
