Overexpression of SIK1 improved hyperglycaemia, hyperlipidaemia and fatty liver, reduced the expression of cAMP-response element binding protein (CREB)-regulated transcription co-activator 2 (CRTC2), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), pS577 SIK1, sterol regulatory element binding-protein-1c (SREBP-1c) and its target genes, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), and increased the expression of SIK1, pT182 SIK1 and pS171 CRTC2 in diabetic rat livers with the suppression of gluconeogenesis and lipid deposition.
In vitro, CVC inhibited CCL2-induced increases in hepatocyte fatty acid synthase (Fasn) and adipose differentiation-related protein (Adrp), whereas it augmented acyl-coenzyme A oxidase 1 (Acox-1), proliferator-activated receptor gamma co-activator alpha (Pgc1α) and uncoupling protein 2 expression, suggesting mechanisms for attenuated hepatocyte steatosis.
In summary, amongst the n3-PUFA, DHA was the most effective for elevating hepatic DHA levels, and preventing progression of hepatic steatosis via reductions in FAS and a marker of fibrosis.
It also reduced expression of the lipogenic genes fatty acid synthase (FAS) and 3-hydroxy-3-methylglutarylCoA reductase (HMGCR), alleviated hepatic steatosis, improved glucose tolerance, elevated insulin sensitivity, and activated insulin receptor substrate (IRS)2/Akt signaling in vivo and/or in vitro.
To investigate [<sup>11</sup>C]acetate PET-surrogate parameter of fatty acid synthase activity-as suitable tool for diagnosis and monitoring of liver steatosis.
It was demonstrated that ChREBP induced FASN ChREBP‑ChoRE binding to accelerate the expression of FASN, leading to hepatocellular steatosis by facilitating H3 and H4 acetylation, H3K4 trimethylation and the phosphorylation of H3S10, but inhibiting the trimethylation of H3K9 and H4K20 in FASN promoter regions of HepG2 and L02 cells.
FK866 significantly promoted liver steatosis in the mice fed with HFD and hepatic lipid accumulation in vitro, accompanied by the increases of the expressions of lipogenic genes such as sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN).
Study 1 focused on regulation by five transcription factors (TFs) (NfKb, Srebp-lc, AMPK, PPARα, PPARγ) of seven, much-studied hepatic long-chain fatty acid (LCFA) transporters (FABPpm, CD36, FATPl, FATP2, FATP4, FATP5, & Caveolin-1 [CAV-1]), and expression of genes for enzymes of LCFA synthesis (SCD-1, FASN) in mice with HS from various causes.
On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice.
Our results suggest that TAM can induce hepatocyte steatosis in vitro and that the enhancement of fatty acid synthesis through the upregulations of SREBP-1c and its downstream target genes (FAS, ACC and SCD) may be the key mechanism of TAM-induced hepatocyte steatosis.
We report here that the development of hepatic steatosis requires IL-1 signaling, which upregulates Fatty acid synthase to promote hepatic lipogenesis.
As far as we know, this is the first line of evidence that demonstrates that HCV infection directly induces FASN expression, and thus suggests a possible mechanism by which HCV infection alters the cellular lipid profile and causes diseases such as steatosis.
The stronger effect of HCV-3a core protein on FAS activation in comparison to HCV-1b core could contribute to the higher prevalence and severity of steatosis in HCV-3a infections.