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Fructose overconsumption impairs hepatic manganese homeostasis and ammonia disposal.
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.
Afiliación
  • Shi JH; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Chen YX; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Feng Y; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Yang X; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
  • Lin J; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
  • Wang T; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Wei CC; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
  • Ma XH; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Yang R; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Cao D; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Zhang H; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Xie X; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
  • Xie Z; NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
  • Zhang WJ; National Key Laboratory of Immunity & Inflammation and Department of Pathophysiology, Naval Medical University, Shanghai, China.
Nat Commun ; 14(1): 7934, 2023 Dec 01.
Article en En | MEDLINE | ID: mdl-38040719
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fructosa / Manganeso Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fructosa / Manganeso Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido