PT  - JOURNAL ARTICLE
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
TI  - Hepatic DKK1-driven steatosis is CD36 dependent
AID  - 10.26508/lsa.202201665
DP  - 2023 Jan 01
TA  - Life Science Alliance
PG  - e202201665
VI  - 6
IP  - 1
4099  - https://www.life-science-alliance.org/content/6/1/e202201665.short
4100  - https://www.life-science-alliance.org/content/6/1/e202201665.full
SO  - Life Sci. Alliance2023 Jan 01; 6
AB  - 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.