Gina Leinninger, Ph.D.
The incidence of obesity-linked diabetes (type-2 diabetes) is increasing worldwide and has accordingly been termed “the diabesity epidemic.” Despite the prevalence of overweight and obesity there are no truly effective pharmacological treatments or cures. Additionally, homeostatic systems regulated by the brain oppose sustained weight loss. Thus, understanding how the brain regulates energy balance and weight is crucial to developing better therapeutics for treatment and prevention of obesity and obesity-linked disease.
The Leinninger Laboratory studies how neurons in the lateral hypothalamic area (LHA) contribute to energy balance and obesity. The LHA is crucial area of the brain for regulating feeding, drinking, sleep and locomotor behaviors that can directly affect weight. Indeed, LHA neurons regulate some of the same brain circuits that mediate reward sensing and addiction (i.e. dopamine neurons.) There are several populations of LHA neurons that differ in their expression of neuropeptides and where they project within the brain (including populations containing neurotensin, orexin, leptin receptor and others) suggesting that these neuronal populations control different aspects of metabolic sensing and physiological output behavior. The goal of our lab is to understand how discrete neuronal populations in the LHA contribute to energy balance and physiology as a whole. We utilize novel mouse models, state-of-the art neuronal tract tracing and neuronal regulation techniques to interrogate LHA neurons and their role in physiology. In particular we examine:
1. What populations of LHA neurons respond to various metabolic stimuli, such as adiposity signals, feeding signals, exercise, etc.?
2. What neurotransmitters and neural pathways are involved?
3. How do LHA neurons regulate motivated behaviors (feeding, drinking, movement etc.) that contribute to energy balance?
4. Can we alter signaling via LHA neurons to promote weight loss or alter physiology?
Collectively, determining how LHA neurons signal and regulate behaviors will increase our understanding of how the brain controls energy balance and the pathogenesis of obesity.