出版社：American Society for Biochemistry and Molecular Biology
摘要：Through a positional cloning approach, the thioredoxin-interacting protein gene (Txnip) was recently identified as causal for a form of combined hyperlipidemia in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J. Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla, P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110–116). We now show that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to fasted mice, including increased levels of plasma ketone bodies and free fatty acids, decreased glucose, and increased hepatic expression of peroxisome proliferator-activated receptor- coactivator-1, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences in the expression of key metabolic enzymes were also observed in other tissues, and the fat-to-muscle ratio of Txnip-deficient mice was increased by 40%. We demonstrate an effect of Txnip on the redox status, as the Txnip-deficient mice in the fed state had a significant increase in the ratio of NADH to NAD+. Surprisingly, we observed that Txnip-deficient mice and wild-type mice had similar levels of thioredoxin activity, suggesting that the effects of Txnip deficiency may be mediated in part by other interactions.
These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status.
Abbreviations: AOX, acyl-CoA oxidase; ECL, enhanced chemiluminescence; Glut2, glucose transporter 2; G6Pase, glucose-6-phosphatase; KH, Krebs-Henseleit; MCAD, medium-chain acyl-CoA dehydrogenase; p-CREB, phosphorylated cAMP response element binding protein; PEPCK, phosphoenolpyruvate carboxykinase; PGC-1, peroxisome proliferator-activated receptor- coactivator-1; SCD1, stearoyl-CoA desaturase 1; SREBP-1c, sterol-response element binding protein-1c; TCA, tricarboxylic acid; TNF, tumor necrosis factor-; Txn, thioredoxin; Txnip, thioredoxin-interacting protein
关键词：redox status • nutritional status • hypoglycemia • hypertriglyceridemia • fatty acid oxidation • mice
