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

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 sign...

Full description

Saved in:
Bibliographic Details
Published in:Molecular metabolism (Germany) 2024-09, Vol.87, p.101984, Article 101984
Main Authors: Buziau, Amée M., Oosterveer, Maaike H., Wouters, Kristiaan, Bos, Trijnie, Tolan, Dean R., Agius, Loranne, Ford, Brian E., Cassiman, David, Stehouwer, Coen D.A., Schalkwijk, Casper G., Brouwers, Martijn C.G.J.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Aldolase B
Animals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism
Carrier Proteins
ChREBP
de novo lipogenesis
Fructose
Fructose-Bisphosphate Aldolase - genetics
Fructose-Bisphosphate Aldolase - metabolism
GKRP
Glucose - metabolism
Glucose signalling
Lipogenesis
Liver - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Original
Transcription Factors - genetics
Transcription Factors - metabolism
Triglycerides - metabolism
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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). 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. Aldob−/− mice showed higher rates of de novo palmitate synthesis from glucose when compared to wildtype mice (p 
ISSN:2212-8778
2212-8778
DOI:10.1016/j.molmet.2024.101984