Mboat7 down-regulation by hyper-insulinemia induces fat accumulation in hepatocytes

BACKGROUND: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. METHODS: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. FINDINGS: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammation and MBOAT7 genotype. Hepatic MBOAT7 levels were reduced in murine models of fatty liver, and by hyper-insulinemia. In wild-type mice, Mboat7 was down-regulated by refeeding and insulin, concomitantly with insulin signalling activation. Acute hepatic Mboat7 silencing promoted hepatic steatosis in vivo and enhanced expression of fatty acid transporter Fatp1. MBOAT7 deletion in hepatocytes reduced the incorporation of arachidonic acid into phosphatidylinositol, consistently with decreased enzymatic activity, determining the accumulation of saturated triglycerides, enhanced lipogenesis and FATP1 expression, while FATP1 deletion rescued the phenotype. INTERPRETATION: MBOAT7 down-regulation by hyper-insulinemia contributes to hepatic fat accumulation, impairing phosphatidylinositol remodelling and up-regulating FATP1. FUNDING: LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02,364,358, Ricerca corrente Fondazione IRCCS Ca\u27 Granda Ospedale Maggiore Policlinico; LV and AG received funding from the European Union Programme Horizon 2020 (No. 777,377) for the project LITMUS- Liver Investigation: Testing Marker Utility in Steatohepatitis . MM was supported by Fondazione Italiana per lo Studio del Fegato (AISF) \u27Mario Coppo\u27 fellowship

Current CaCO3 dissolution at the seafloor caused by anthropogenic CO2

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152452/1/pnas_2018_CaCO3_dissolution_sulpisetal.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152452/2/pnas_2018_CaCO3_dissolution_sulpisetal_SupportingMaterial.pdfDescription of pnas_2018_CaCO3_dissolution_sulpisetal.pdf : Main articleDescription of pnas_2018_CaCO3_dissolution_sulpisetal_SupportingMaterial.pdf : Supporting materia

Low-lying dipole response in the unstable Ni 70 nucleus

The Coulomb excitation of the neutron-rich nucleus Ni70 was measured in inverse kinematics at 260AMeV bombarding energy and with a Au197 target. The beam energy allowed us to study the dipole response around the neutron separation energy (up to about 12 MeV). The experiment was performed at the RIKEN Radioactive Isotope Beam Factory (RIBF). The γ decay from the scattered Ni70 ions at around zero degree was measured with a scintillator detection system composed of large volume LaBr3:Ce detectors (HECTOR+ array) and NaI(Tl) detectors (DALI2 array). Results were obtained for the E1 strength in the region where the dipole response is characterized by the presence of the pygmy dipole resonance. The measured E1 strength is found to be larger as compared with that of Ni68 below the neutron binding energy. The measured E1 strength as a function of energy is compared with available predictions based on relativistic and nonrelativistic approaches, and only in some cases does theory give a reasonable account of the data