Alterations of hepatic energy metabolism in murine models of obesity, diabetes and fatty liver diseases

Disturbed hepatic energy metabolism contributes to non-alcoholic fatty liver (NAFLD), but the development of changes over time and obesity- or diabetes-related mechanisms remained unclear. Two-day old male C57BL/6j mice received streptozotocin (STZ) or placebo (PLC) and then high-fat (HFD) or regula...

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Published in:EBioMedicine 2023-08, Vol.94, p.104714-104714, Article 104714
Main Authors: Dewidar, Bedair, Mastrototaro, Lucia, Englisch, Cornelia, Ress, Claudia, Granata, Cesare, Rohbeck, Elisabeth, Pesta, Dominik, Heilmann, Geronimo, Wolkersdorfer, Martin, Esposito, Irene, Reina Do Fundo, Michelle, Zivehe, Fariba, Yavas, Aslihan, Roden, Michael
Format: Article
Language:English
Subjects:
Fatty liver
High-resolution respirometry
Insulin resistance
Mitochondria
Type 1 diabetes
Type 2 diabetes
Unfolded protein response
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Summary:Disturbed hepatic energy metabolism contributes to non-alcoholic fatty liver (NAFLD), but the development of changes over time and obesity- or diabetes-related mechanisms remained unclear. Two-day old male C57BL/6j mice received streptozotocin (STZ) or placebo (PLC) and then high-fat (HFD) or regular chow diet (RCD) from week 4 (W4) to either W8 or W16, yielding control [CTRL = PLC + RCD], diabetes [DIAB = STZ + RCD], obesity [OBES = PLC + HFD] and diabetes-related non-alcoholic steatohepatitis [NASH = STZ + HFD] models. Mitochondrial respiration was measured by high-resolution respirometry and insulin-sensitive glucose metabolism by hyperinsulinemic-euglycemic clamps with stable isotope dilution. NASH showed higher steatosis and NAFLD activity already at W8 and liver fibrosis at W16 (all p 
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2023.104714