Hepatic steatosis is a core feature of the metabolic syndrome and type 2 diabetes and leads to hepatic insulin resistance. Malonyl-CoA, generated by acetyl-CoA carboxylases 1 and 2 (Acc1 and Acc2), ...is a key regulator of both mitochondrial fatty acid oxidation and fat synthesis. We used a diet-induced rat model of nonalcoholic fatty liver disease (NAFLD) and hepatic insulin resistance to explore the impact of suppressing Acc1, Acc2, or both Acc1 and Acc2 on hepatic lipid levels and insulin sensitivity. While suppression of Acc1 or Acc2 expression with antisense oligonucleotides (ASOs) increased fat oxidation in rat hepatocytes, suppression of both enzymes with a single ASO was significantly more effective in promoting fat oxidation. Suppression of Acc1 also inhibited lipogenesis whereas Acc2 reduction had no effect on lipogenesis. In rats with NAFLD, suppression of both enzymes with a single ASO was required to significantly reduce hepatic malonyl-CoA levels in vivo, lower hepatic lipids (long-chain acyl-CoAs, diacylglycerol, and triglycerides), and improve hepatic insulin sensitivity. Plasma ketones were significantly elevated compared with controls in the fed state but not in the fasting state, indicating that lowering Acc1 and -2 expression increases hepatic fat oxidation specifically in the fed state. These studies suggest that pharmacological inhibition of Acc1 and -2 may be a novel approach in the treatment of NAFLD and hepatic insulin resistance.
The XENON100 experiment, in operation at the Laboratori Nazionali del Gran Sasso in Italy, is designed to search for dark matter weakly interacting massive particles (WIMPs) scattering off 62 kg of ...liquid xenon in an ultralow background dual-phase time projection chamber. In this Letter, we present first dark matter results from the analysis of 11.17 live days of nonblind data, acquired in October and November 2009. In the selected fiducial target of 40 kg, and within the predefined signal region, we observe no events and hence exclude spin-independent WIMP-nucleon elastic scattering cross sections above 3.4 × 10⁻⁴⁴ cm² for 55 GeV/c² WIMPs at 90% confidence level. Below 20 GeV/c², this result constrains the interpretation of the CoGeNT and DAMA signals as being due to spin-independent, elastic, light mass WIMP interactions.
We report an early result from the ICARUS experiment on the search for a
ν
μ
→
ν
e
signal due to the LSND anomaly. The search was performed with the ICARUS T600 detector located at the Gran Sasso ...Laboratory, receiving CNGS neutrinos from CERN at an average energy of about 20 GeV, after a flight path of ∼730 km. The LSND anomaly would manifest as an excess of
ν
e
events, characterized by a fast energy oscillation averaging approximately to
with probability
. The present analysis is based on 1091 neutrino events, which are about 50 % of the ICARUS data collected in 2010–2011. Two clear
ν
e
events have been found, compared with the expectation of 3.7±0.6 events from conventional sources. Within the range of our observations, this result is compatible with the absence of a LSND anomaly. At 90 % and 99 % confidence levels the limits of 3.4 and 7.3 events corresponding to oscillation probabilities
and
are set respectively. The result strongly limits the window of open options for the LSND anomaly to a narrow region around (Δ
m
2
,sin
2
(2
θ
))
new
=(0.5 eV
2
,0.005), where there is an overall agreement (90 % CL) between the present ICARUS limit, the published limits of KARMEN and the published positive signals of LSND and MiniBooNE Collaborations.
Our recent studies of very short gamma-ray bursts (GRBs) of T sub(90) , 100 ms duration have indicated a significant angular asymmetry and a uniform V/V sub(max) distribution from the BATSE (Burst ...and Transient Source Experiment on the Compton Gamma Ray Observatory CGRO) data. Here we update these studies, and we extend our research to events observed with Konus, a GRB experiment from Russia on the International Solar Terrestrial Physics/Wind satellite, that gives us new insight into the spectra that was not possible with the BATSE data. Konus has observed 18 events with T sub(90) , 100 ms duration. These events display a considerable number of photons with energies above 1 MeV and have photons above 5 MeV in all cases. These appear to be some of the most energetic photons observed from any class of GRB to date.
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