Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications.

Autophagy is a lysosomal degradative pathway critical for the removal and breakdown of cellular components such as organelles and proteins. Despite striking similarities in the regulation and function of autophagy and lipid metabolism, the two processes have only recently been shown to be interrelated. This review details new findings of critical functions for autophagy in lipid metabolism and storage. Studies in hepatocytes and liver have demonstrated that macroautophagy mediates the breakdown of lipids stored in lipid droplets and that an inhibition of autophagy leads to the development of a fatty liver. In contrast, in adipocytes the loss of macroautophagy decreases the amount of lipid stored in adipose tissue through effects on white and brown adipocyte differentiation. Other investigations have indicated that the relationship between autophagy and lipids is bidirectional, with changes in cellular lipid content altering autophagic function. These newly described links between autophagy and lipid metabolism and storage have provided new insights into the mechanisms of both processes. The findings also suggest possible new therapeutic approaches to the problems of lipid overaccumulation and impaired autophagy that occur with aging and the metabolic syndrome.