(For previous entries, see days one, two, and three.)
Very smelly morning, often about innate smell detection, but a significant portion of the works were already published. In the afternoon, a couple taste talks caught my eye.
I'm a fan of Ninomiya's work, having covered his papers on leptin and cannabinoid modulation of sweet taste previously. Here, he provided an update to that work, concentrating on the relative strengths of leptin vs cannabinoids. In WT mice, cannabinoid antagonists are ineffective, while leptin antagonists are. However, in db/db mice (leptin knockouts) cannabinoid antagonists do reduce sweet responses in the CT nerve. Thus it appears that under normal conditions leptin is dominant. To verify this, they measured sweet responses in mice with varied blood leptin levels, and found that cannabinoid antagonists became more effective as leptin levels went down.
Besides being sensed by the tongue, sugar is also detected by the stomach, which influences food intake over longer time scales. Sclafani's lab investigated this by directly injecting sucrose into the mouse gut (? Or IP) in T1R2 knockout mice (no canonical sweet receptor). Mice triggered the injection by licking a water spout. They employed a conditioning protocol, where unsweetened cherry taste caused sugar water injection, while grape taste caused water injection. After conditioning, mice licked the cherry water more.
Sclafani mentioned three possible receptors: GLUT5 which can detect fructose but not galactose; and SGLT1/5 which can detect galactose but not fructose. To see which of these are involved, they switched the injection to fructose or galactose. Mice injected with fructose were not conditioned, showing GLUT5 is not responsible. In contrast , galactose did work for conditioning. To see whether metabolization is necessary they tried conditioning with MDG, a non-metabolizable galactose analog, and found conditioning still worked. Thus SGLT activation alone seems to be sufficient.
How could this signal downstream? Scalfani noted that most gut hormones decrease food intake, while ghrelin, the one orexigenic hormone, is suppressed by glucose. Thus there is at the moment no clear pathway for the effect.