Role of hypothalamic autophagy in the control of whole body energy balance.

Autophagy is a catabolic process involving the rearrangement of subcellular membranes to sequester cytoplasm and organelles for delivery to lysosomes, where the sequestered material is degraded and recycled. Autophagy is important for maintenance of intracellular energy homeostasis and the quality control of organelles such as the endoplasmic reticulum (ER) and mitochondria, which suggests that dysregulated autophagy might play a role in the pathogenesis of metabolic disorders and diabetes. In an attempt to elucidate the role of autophagy in metabolic disorders, diverse in vivo and in vitro models have been employed. Site-specific autophagy knockout models that are autophagy-deficient specifically in pancreatic ß-cells, skeletal muscle, adipose tissues or liver have been produced. These models have generated valuable information regarding the role of autophagy in body metabolism. The role of autophagy in the hypothalamus, which controls whole body energy balance, appetite and energy expenditure, has also been investigated. Thus, mice with autophagy deficiency in the hypothalamus have shown diverse phenotypes (lean vs. obese) depending on the site of autophagy deficiency or the method of autophagy abrogation.