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. Author manuscript; available in PMC: 2010 Jul 22.
Published in final edited form as: Semin Liver Dis. 2008 Oct 27;28(4):360–369. doi: 10.1055/s-0028-1091980

Figure 1.

Figure 1

Free fatty acids (FFAs) induce hepatocyte apoptosis. FFAs can modulate both the extrinsic and the intrinsic pathways of hepatocyte apoptosis. The saturated fatty acids, palmitic acid and stearic acid, lead to c-jun N-terminal kinase (JNK) dependent activation of the proapoptotic protein Bax, which then leads to mitochondrial permeabilization with release of cytochrome c, activation of effector caspases, and apoptosis. Palmitic acid can also activate the lysosomal pathway of apoptosis, via Bax activation and Bax-dependent lysosomal permeabilization. Furthermore, palmitic acid and stearic acid activate protein phosphatase 2A (PP2A) leading to activation of FoxO3a, and transcriptional activation of the proapoptotic protein Bim. The monounsaturated fatty acid, oleic acid, which is minimally toxic per se, imparts sensitivity to the death receptor mediated extrinsic pathway of apoptosis. Fas and TRAIL-R2 expression is induced by oleic acid treatment. TRAIL-R2 expression is under the transcriptional control of JNK in oleic acid treated cells. This sensitizes fatty hepatocytes to circulating Fas or TRAIL.