Rajat Singh, M.D., M.B.,B.S.

Autophagy or “self-eating” is an in-bulk lysosomal degradative pathway that plays a crucial role in cellular homeostasis through protein and organelle turnover. Autophagy occurs at basal levels in all cells and is induced following conditions such as stress or nutrient-deprivation. Briefly, the process of autophagy requires the de novo formation of a double-walled limiting membrane that engulfs cellular cargo destined for degradation and then seals upon itself to form an autophagosome. The delivery of the engulfed cargo to the lysosome occurs by fusion of the autophagosome with the lysosome leading to degradation of the cargo. We have recently demonstrated a novel role of autophagy in the mobilization and degradation of intracellular lipid stores in the liver, thus pointing to a possible function of autophagy in energy homeostasis. We have also recently shown that this lipophagic role of autophagy functions in hypothalamic neurons to generate neuron-intrinsic free acids that, in turn, drive neuronal feeding mechanisms.

The primary focus of the lab 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:

     1. Roles for autophagy in discrete hypothalamic neurons in food intake and energy balance

     2. Signaling mechanisms modulating autophagy in hypothalamic neurons

     3. Metabolic and regulatory functions of autophagy in adipose biology 

Aging is considered to reduce autophagic activity. The second focus of the laboratory is to examine the effect of aging-induced reduction of hypothalamic and adipose autophagy on the development of the metabolic syndrome of aging.