FoxO transcription factors regulate urea cycle through Ass1.

Autor: Karkoutly S; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Takeuchi Y; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Mehrazad Saber Z; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan., Ye C; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Tao D; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Aita Y; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Murayama Y; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Shikama A; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Masuda Y; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Izumida Y; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Matsuzaka T; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Kawakami Y; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Shimano H; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan., Yahagi N; Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical University, Tochigi, 329-0498, Japan; Nutrigenomics Research Group, Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan; Department of Internal Medicine (Endocrinology and Metabolism), Institute of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan. Electronic address: nyahagi-tky@umin.ac.jp.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Dec 20; Vol. 739, pp. 150594. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.bbrc.2024.150594
Abstrakt: When amino acids are plentiful in the diet, the liver upregulates most enzymes responsible for amino acid degradation. In particular, the activity of urea cycle enzymes increases in response to high-protein diets to facilitate the excretion of excess nitrogen. KLF15 has been established as a critical regulator of amino acid catabolism including ureagenesis and we have recently identified FoxO transcription factors as an important upstream regulator of KLF15 in the liver. Therefore, we explored the role of FoxOs in amino acid metabolism under high-protein diet. Our findings revealed that the concentrations of two urea cycle-related amino acids, arginine and ornithine, were significantly altered by FoxOs knockdown. Additionally, using KLF15 knockout mice and an in vivo Ad-luc analytical system, we confirmed that FoxOs directly regulate hepatic Ass1 expression under high-protein intake independently from KLF15. Moreover, ChIP analysis showed that the high-protein diet increased FoxOs DNA binding without altering the nuclear protein amount. Therefore, FoxOs play a direct role in regulating ureagenesis via a KLF15-independent pathway in response to high-protein intake.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: