TY - JOUR T1 - Hepatic DKK1-driven steatosis is CD36 dependent JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201665 VL - 6 IS - 1 SP - e202201665 AU - Zhen Yang AU - Xinping Huang AU - Jiaye Zhang AU - Kai You AU - Yue Xiong AU - Ji Fang AU - Anteneh Getachew AU - Ziqi Cheng AU - Xiaorui Yu AU - Yan Wang AU - Feima Wu AU - Ning Wang AU - Shufen Feng AU - Xianhua Lin AU - Fan Yang AU - Yan Chen AU - Hongcheng Wei AU - Yin-xiong Li Y1 - 2023/01/01 UR - https://www.life-science-alliance.org/content/6/1/e202201665.abstract N2 - Nonalcoholic fatty liver disease (NAFLD) is prevalent worldwide; about 25% of NAFLD silently progress into steatohepatitis, in which some of them may develop into fibrosis, cirrhosis and liver failure. However, few drugs are available for NAFLD, partly because of an incomplete understanding of its pathogenic mechanisms. Here, using in vivo and in vitro gain- and loss-of-function approaches, we identified up-regulated DKK1 plays a pivotal role in high-fat diet–induced NAFLD and its progression. Mechanistic analysis reveals that DKK1 enhances the capacity of hepatocytes to uptake fatty acids through the ERK-PPARγ-CD36 axis. Moreover, DKK1 increased insulin resistance by activating the JNK signaling, which in turn exacerbates disorders of hepatic lipid metabolism. Our finding suggests that DKK1 may be a potential therapeutic and diagnosis candidate for NAFLD and metabolic disorder progression. ER -