Quercetin Reduces Lipid Accumulation in a Cell Model of NAFLD by Inhibiting De Novo Fatty Acid Synthesis through the Acetyl‐CoA Carboxylase 1/AMPK/PP2A Axis

none6noDysregulation of de novo lipogenesis (DNL) has recently gained strong attention as being one of the critical factors that contribute to the assessment of non‐alcoholic fatty liver disease (NAFLD). NAFLD is often diagnosed in patients with dyslipidemias and type 2 diabetes; thus, an interesting correlation can be deduced between high hematic free fatty acids and glucose excess in the DNL dysregulation. In the present study, we report that, in a cellular model of NAFLD, the coexistence of elevated glucose and FFA conditions caused the highest cellular lipid accumulation. Deepening the molecular mechanisms of the DNL dysregulation—RT‐qPCR and immunoblot analysis demonstrated increased expression of mitochondrial citrate carrier (CiC), cytosolic acetyl‐ CoA carboxylase 1 (ACACA), and diacylglycerol acyltransferase 2 (DGAT2) involved in fatty acids and triglycerides synthesis, respectively. XBP‐1, an endoplasmic reticulum stress marker, and SREBP‐1 were the transcription factors connected to the DNL activation. Quercetin (Que), a flavonoid with strong antioxidant properties, and noticeably reduced the lipid accumulation and the expression of SREBP‐1 and XBP‐1, as well as of their lipogenic gene targets in steatotic cells. The anti‐lipogenic action of Que mainly occurs through a strong phosphorylation of ACACA, which catalyzes the committing step in the DNL pathway. The high level of ACACA phosphorylation in Que‐treated cells was explained by the intervention of AMPK together with the reduction of enzymatic activity of PP2A phosphatase. Overall, our findings highlight a direct anti‐lipogenic effect of Que exerted through inhibition of the DNL pathway by acting on ACACA/AMPK/PP2A axis; thus, suggesting this flavonoid as a promising molecule for the NAFLD treatment.openGnoni A.; Di Chiara Stanca B.; Giannotti L.; Gnoni G.V.; Siculella L.; Damiano F.Gnoni, A.; Di Chiara Stanca, B.; Giannotti, L.; Gnoni, G. V.; Siculella, L.; Damiano, F

Search for High-energy Neutrinos from Binary Neutron Star Merger GW170817 with ANTARES, IceCube, and the Pierre Auger Observatory

The Advanced LIGO and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst (GRB) that followed the merger of this binary was also recorded by the Fermi Gamma-ray Burst Monitor (Fermi-GBM), and the Anticoincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the GeV--EeV energy range using the ANTARES, IceCube, and Pierre Auger Observatories. No neutrinos directionally coincident with the source were detected within $\pm500$ s around the merger time. Additionally, no MeV neutrino burst signal was detected coincident with the merger. We further carried out an extended search in the direction of the source for high-energy neutrinos within the 14-day period following the merger, but found no evidence of emission. We used these results to probe dissipation mechanisms in relativistic outflows driven by the binary neutron star merger. The non-detection is consistent with model predictions of short GRBs observed at a large off-axis angle.Comment: 22 pages, 2 figure