RT Journal Article
SR Electronic
T1 Hepatic DKK1-driven steatosis is CD36 dependent
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201665
DO 10.26508/lsa.202201665
VO 6
IS 1
A1 Yang, Zhen
A1 Huang, Xinping
A1 Zhang, Jiaye
A1 You, Kai
A1 Xiong, Yue
A1 Fang, Ji
A1 Getachew, Anteneh
A1 Cheng, Ziqi
A1 Yu, Xiaorui
A1 Wang, Yan
A1 Wu, Feima
A1 Wang, Ning
A1 Feng, Shufen
A1 Lin, Xianhua
A1 Yang, Fan
A1 Chen, Yan
A1 Wei, Hongcheng
A1 Li, Yin-xiong
YR 2023
UL http://www.life-science-alliance.org/content/6/1/e202201665.abstract
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.