Figure 2.

Schematic model represents the molecular mechanisms and dysregulation of autophagy components in a high-fat diet (HFD)/obesity-induced impaired autophagic function in NAFLD. HFD-/obesity-mediated activation of SIRT3 inactivates AMPK, mTORC1, and ULK1 complex leading to inhibition of phagophore formation. A high fatty acid diet upregulates Rubicon expression, increasing its interaction with Beclin 1 and decreasing autophagosome-lysosome fusion. HFD/obesity decreases the expression and activities of cathepsin family enzymes and downregulates autolysosomal proteolysis. HFD/obesity induces changes in the membrane lipid composition of the lysosome, affects autophagosomal-lysosomal acidification, and inhibits fusion of the autophagosome with the lysosome.