Hepatic glucokinase regulatory protein and carbohydrate response element binding protein attenuation reduce de novo lipogenesis but do not mitigate intrahepatic triglyceride accumulation in Aldob deficiency

Autor: Amée M. Buziau, Maaike H. Oosterveer, Kristiaan Wouters, Trijnie Bos, Dean R. Tolan, Loranne Agius, Brian E. Ford, David Cassiman, Coen D.A. Stehouwer, Casper G. Schalkwijk, Martijn C.G.J. Brouwers
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Metabolism, Vol 87, Iss , Pp 101984- (2024)
Druh dokumentu: article
ISSN: 2212-8778
DOI: 10.1016/j.molmet.2024.101984
Popis: Objective: Stable isotope studies have shown that hepatic de novo lipogenesis (DNL) plays an important role in the pathogenesis of intrahepatic lipid (IHL) deposition. Furthermore, previous research has demonstrated that fructose 1-phosphate (F1P) not only serves as a substrate for DNL, but also acts as a signalling metabolite that stimulates DNL from glucose. The aim of this study was to elucidate the mediators of F1P-stimulated DNL, with special focus on two key regulators of intrahepatic glucose metabolism, i.e., glucokinase regulatory protein (GKRP) and carbohydrate response element binding protein (ChREBP). Methods: Aldolase B deficient mice (Aldob−/−), characterized by hepatocellular F1P accumulation, enhanced DNL, and hepatic steatosis, were either crossed with GKRP deficient mice (Gckr−/−) or treated with short hairpin RNAs directed against hepatic ChREBP. Results: Aldob−/− mice showed higher rates of de novo palmitate synthesis from glucose when compared to wildtype mice (p
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