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. Author manuscript; available in PMC: 2018 May 1.
Published in final edited form as: Hepatology. 2018 Apr 6;67(5):2013–2024. doi: 10.1002/hep.29689

Fig. 4. High fat diet induced JNK activation in hepatocytes, Kupffer cells and adipocytes in the development of NAFLD and NASH.

Fig. 4

JNK signaling in hepatocytes inhibits insulin signaling and causes insulin resistance. Sustained JNK1/2 activation upregulates PPARα-corepressor NcoR1 which in turn inhibits PPARα-responsive gene transcription. Both JNK1 and JNK2 participate in the regulation of NcoR1 in hepatocytes. PPARα regulates Fgf21 expression. Serum FGF21 activates adipocyte PGC1α and inhibits PPARγ and downstream target genes. P-JNK1 in adipocytes activates adipokines expression including IL-6 which targets hepatocytes to increase SOCS3. SOCS3 inhibits insulin signaling in hepatocytes and many other cells. JNK1/2 regulates M1 macrophage differentiation, tissue infiltration, and release of cytokines including TNF.