Session: SUN 0345-0362-Growth Factor/ Tyrosine Kinase signaling, Inhibin/Activin Superfamily, Cell Regulation
Poster Board SUN-0346
Outstanding Abstract Award
Abstract The oxidized nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 plays an essential role in hepatic fatty acid and glucose metabolism, which is related to steatosis and glucose intolerance in obese mice. Up to now, the detailed underlying mechanism is largely unknown. RNA binding protein QKI is a recently identified important molecule in cell growth and metabolism. Here we first found that hepatic QKI was acetylated under feeding conditions, while it was deacetylated by SIRT1 under fasting conditions. Knockdown of QKI under fasting conditions resulted in compromised gluconeogenesis and fatty acid oxidation, while the effects on metabolism under feeding conditions were much milder, indicating that QKI plays an essential role in metabolism under fasting conditions. Compared with acetylated QKI, deacytelated QKI had higher affinity with the downstream targets, such as PPARα and FOXO1. Interaction between QKI and PPARα/ FOXO1 in turn increased the expression of these target genes both at mRNA and protein levels. Accordingly, the downstream metabolism related genes of PPARα and FOXO1, such as G6P (Glucose-6-phosphatase), PEPCK2 (Phosphoenolpyruvate carboxykinase 2), ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain), CPT1A (Carnitine palmitoyltransferase I A ), HMGCS2 (3-hydroxy-3-methylglutaryl- CoA synthase 2) were increased by QKI expression, with the trend much more obvious under fasting conditions or by directly forced expression of the acetylated analogue. Taken together, our study here reveals that deacetylation of RNA binding protein QKI by SIRT1 under fasting conditions controls the adaptive hepatic energy metabolism.
Nothing to Disclose: XL, GY, ZL
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