Autophagy plays a key role in cellular homeostasis since it allows optimal cellular functioning and provides energy under conditions of stress. Initial is revealed that alterations of macroautophagy disturb adipogenic differentiation in cultured cells, and in mice, leading to a drastic reduction of adipose tissue depots. Nevertheless, more recent studies indicate that autophagy participates in the control of adipose tissue biology in a more complex manner. The protein TP53INP2 activates the formation of autophagosomes by binding to ATG8 proteins such as LC3 or GATE16, and its genetic elimination reduces but does not cancel this activity. TP53INP2 deficiency increases adipogenic differentiation and induces a gain in adiposity in the mouse. At the cellular level, TP53INP2 promotes the sequestration of the regulatory protein GSK3β in multivesicular bodies (MVBs) by a process that involves autophagic activity and the participation of the endosomal sorting complexes required for transport (ESCRT) machinery. Through this mechanism, TP53INP2 stabilizes and activates β-catenin, which in turn triggers the inhibition of adipogenesis. In summary, autophagic pathways provide a whole set of mechanisms that may regulate in an opposite way the biology of adipose tissue, and consequently, have a variable impact on the whole body adiposity. This concept may be extensible to other cell types.
Keywords: AUTOPHAGY; adipogenesis; obesity.