We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal.
- Authors
Shi, Jian-Hui; Chen, Yu-Xia; Feng, Yingying; Yang, Xiaohang; Lin, Jie; Wang, Ting; Wei, Chun-Chun; Ma, Xian-Hua; Yang, Rui; Cao, Dongmei; Zhang, Hai; Xie, Xiangyang; Xie, Zhifang; Zhang, Weiping J.
- Abstract
Arginase, a manganese (Mn)-dependent enzyme, is indispensable for urea generation and ammonia disposal in the liver. The potential role of fructose in Mn and ammonia metabolism is undefined. Here we demonstrate that fructose overconsumption impairs hepatic Mn homeostasis and ammonia disposal in male mice. Fructose overexposure reduces liver Mn content as well as its activity of arginase and Mn-SOD, and impairs the clearance of blood ammonia under liver dysfunction. Mechanistically, fructose activates the Mn exporter Slc30a10 gene transcription in the liver in a ChREBP-dependent manner. Hepatic overexpression of Slc30a10 can mimic the effect of fructose on liver Mn content and ammonia disposal. Hepatocyte-specific deletion of Slc30a10 or ChREBP increases liver Mn contents and arginase activity, and abolishes their responsiveness to fructose. Collectively, our data establish a role of fructose in hepatic Mn and ammonia metabolism through ChREBP/Slc30a10 pathway, and postulate fructose dietary restriction for the prevention and treatment of hyperammonemia. Manganese is an essential trace element for the activity of arginase in the process of urea generation and ammonia disposal in the liver. Here, the authors show that fructose overconsumption impairs hepatic Mn homeostasis and ammonia disposal in male mice.
- Subjects
FRUCTOSE; AMMONIA; MANGANESE; HOMEOSTASIS; UREA; ARGINASE; TRACE elements
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-43609-0