Coffee modulates insulin-hepatocyte nuclear factor-4α-Cyp7b1 pathway and reduces oxysterol-driven liver toxicity in a nonalcoholic fatty liver disease mouse model
Genta Kakiyama, Kei Minowa, Daniel Rodríguez‐Agudo, Rebecca Martin, Hajime Takei, Kuniko Mitamura, Shigeo Ikegawa, Mitsuyoshi Suzuki, Hiroshi Nittono, Michael Fuchs, Douglas M. Heuman, Huiping Zhou, William M. Pandak
Abstract
This study demonstrated dietary coffee prevented the accumulation of hepatic oxysterols by maintaining Cyp7b1/Sult2b1 expression in a diet-induced NAFLD mice model. Lowering liver oxysterols markedly reduced inflammation in the coffee-ingested mice. Caffeine is not fundamental to this effect. In addition, this study showed Cyp7b1/Sult2b1 responses to insulin signaling can be mediated through a transcriptional factor, HNF4α. The insulin-HNF4α-Cyp7b1/Sult2b1 signaling pathway, which directly correlates to the onset of NASH triggered by insulin resistance, offers insight into approaches for NAFLD treatment.