Overexpression of Fto leads to increased food intake and results in obesity

Genome-wide association studies have identified SNPs within FTO, the human fat mass and obesity-associated gene, that are strongly associated with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh, on average, ~3 kg more than individuals with the low-risk T allele. Mice that lack FTO function and/or Fto expression display increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or a high-fat diet. Our results suggest that increased body mass results primarily from increased food intake. Mice with increased Fto expression on a high-fat diet develop glucose intolerance. This study provides the first direct evidence that increased Fto expression causes obesity in mice.     

Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic beta-cells

Glucose stimulates insulin secretion from the pancreatic beta-cell by increasing the cytosolic calcium concentration. It is believed that this increment results mainly from Ca2+ influx through dihydropyridine-sensitive calcium channels because insulin secretion is abolished by dihydropyridine antagonists and is potentiated by dihydropyridine agonists. Glucose may influence Ca2+ influx through these channels in two ways: either by regulating the beta-cell membrane potential or by biochemical modulation of the channel itself. The former mechanism is well established. Glucose metabolism, by closing ATP-sensitive K+ channels, depolarizes the beta-cell membrane and initiates Ca2+-dependent electrical activity, with higher glucose concentrations further increasing Ca2+ influx by raising the frequency of action potentials. We show here that glucose metabolism also increases calcium influx directly, by modulating the activity of dihydropyridine-sensitive Ca2+ channels.     

Structure and bandgap closure in dense hydrogen

The possibility that steadily compressed hydrogen might undergo a transition from a proton-paired insulator to a monatomic metal was first suggested in 1935. But experimental realization of metallic hydrogen in solid form has remained elusive, despite studies at pressures as high as 342 GPa. The pairing structure is known to be robust (from the persistence of its associated vibron mode), leading to the suggestion of an alternative route to the metallic state, involving a band-overlap transition in which the pairing is preserved. Here we report density functional calculations within the local density approximation that predict a range of densities for hydrogen where a paired or molecular metallic state may be energetically preferred. The transition to this metallic state is naturally associated with the closing of an overall bandgap; but the pressures required to effect the transition are shown to change significantly when the gaps are corrected by approximate inclusion of many-electron effects. The implication is that a complete resolution of the structural and phase problem in dense hydrogen may require methods beyond the local density approximation.