Inhibiting mitochondrial citrate shuttling induces hepatic triglyceride deposition in Nile tilapia (Oreochromis niloticus) through lipid anabolic remodeling.

Autor: Wang JX; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Luo Y; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Limbu SM; Department of Aquaculture Technology, School of Aquatic Sciences and Fisheries Technology, University of Dar es Salaam, Dar es Salaam, Tanzania., Qian YC; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Zhang YY; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Li RX; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Zhou WH; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Qiao F; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Chen LQ; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Zhang ML; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China., Du ZY; LANEH, Department of Zoology, School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: zydu@bio.ecnu.edu.cn.
Jazyk: angličtina
Zdroj: The Journal of nutritional biochemistry [J Nutr Biochem] 2024 Sep; Vol. 131, pp. 109678. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1016/j.jnutbio.2024.109678
Abstrakt: The solute carrier family 25 member 1 (Slc25a1)-dependent mitochondrial citrate shuttle is responsible for exporting citrate from the mitochondria to the cytoplasm for supporting lipid biosynthesis and protein acetylation. Previous studies on Slc25a1 concentrated on pathological models. However, the importance of Slc25a1 in maintaining metabolic homeostasis under normal nutritional conditions remains poorly understood. Here, we investigated the mechanism of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis in male Nile tilapia (Oreochromis niloticus). To achieve the objective, we blocked the mitochondrial citrate shuttle by inhibiting Slc25a1 under normal nutritional conditions. Slc25a1 inhibition was established by feeding Nile tilapia with 250 mg/kg 1,2,3-benzenetricarboxylic acid hydrate for 6 weeks or intraperitoneal injecting them with dsRNA to knockdown slc25a1b for 7 days. The Nile tilapia with Slc25a1 inhibition exhibited an obesity-like phenotype accompanied by fat deposition, liver damage and hyperglycemia. Moreover, Slc25a1 inhibition decreased hepatic citrate-derived acetyl-CoA, but increased hepatic triglyceride levels. Furthermore, Slc25a1 inhibition replenished cytoplasmic acetyl-CoA through enhanced acetate pathway, which led to hepatic triglycerides accumulation. However, acetate-derived acetyl-CoA caused by hepatic Slc25a1 inhibition did not activate de novo lipogenesis, but rather modified protein acetylation. In addition, hepatic Slc25a1 inhibition enhanced fatty acids esterification through acetate-derived acetyl-CoA, which increased Lipin1 acetylation and its protein stability. Collectively, our results illustrate that inhibiting mitochondrial citrate shuttle triggers lipid anabolic remodeling and results in lipid accumulation, indicating the importance of mitochondrial citrate shuttle in maintaining lipid metabolism homeostasis.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: