We demonstrated a role for autophagy in mobilization and degradation of intracellular lipid stores by a process we termed lipophagy, thus mapping autophagy to metabolic regulation. We have recently shown that lipophagy in hypothalamic neurons generates neuron-intrinsic free fatty acids that drive neuronal feeding mechanisms.
The primary research focus of the laboratory is to examine the organ-specific roles of autophagy in the regulation of lipid metabolism and energy homeostasis using biochemical, immunochemical, and image-based approaches in vitro and in conditional knockout mouse models. We are interested in understanding how hypothalamic autophagy controls energy expenditure in peripheral tissues by influencing lipid metabolism and tissue differentiation in peripheral tissues.
The second research focus of the laboratory is to examine the consequences of aging-associated reduction of autophagy on the development of the metabolic syndrome of aging. We are currently interested in understanding how autophagy decreases with age, and whether restoration of autophagy prevents the development of the metabolic syndrome of aging.
Our long term goals are to generate means to activate autophagy to prevent diabetes and improve the health-span in the aging population.
OUR SPECIFIC QUESTIONS ARE:
1. How does hypothalamic autophagy control food intake and energy expenditure?
2. How does nutrient-related signals modify autophagy?
3. What are the roles for autophagy in adipocytes and adipose progenitors in fuel utilization?
4. How does autophagy decrease with age?
5. Can we prevent the metabolic syndrome and improve health-span by activating autophagy?