Autophagy in Adipose Tissue Physiology and Pathophysiology.

Significance: Alterations in adipose tissue function have profound consequences on whole body energy homeostasis because this tissue is central for fat accumulation, energy expenditure, glucose and insulin metabolism, and hormonal regulation. With the obesity reaching epidemic proportions globally, it is important to understand the mechanisms leading to adipose tissue malfunction. Recent Advances: Autophagy has originally been viewed as an adaptive response to cellular stress, but in recent years this process was shown to regulate important cellular processes. In adipose tissue, autophagy is a key regulator of white adipose tissue (WAT) and brown adipose tissue (BAT) adipogenesis, and dysregulated autophagy impairs fat accumulation both in vitro and in vivo. Animal studies have also suggested an important role for autophagy and mitophagy during the transition from beige to white fat. Human studies have provided evidence for altered autophagy in WAT, and these alterations correlated with the degree of insulin resistance. Critical Issues: Despite these important advances in the study of autophagy in adipose tissue, we still do not understand the physiological role of autophagy in mature white and brown adipocytes. Furthermore, several human studies involving autophagy assessment were performed on whole adipose tissue, which complicates the interpretation of the results considering the cellular heterogeneity of this tissue. Future Directions: Future studies will undoubtedly expand our understanding of the role of autophagy in fully differentiated adipocytes, and uncover novel cross-talks between this tissue and other organs in regulating lipid metabolism, redox signaling, energy homeostasis, and insulin sensitivity.