Supplementary Material for: Anorexigenic and Orexigenic Hormone Modulation of Mammalian Target of Rapamycin Complex 1 Activity and the Regulation of Hypothalamic Agouti-Related Protein mRNA Expression

Activation of mammalian target of rapamycin 1 (mTORC1) by nutrients, insulin and leptin leads to appetite suppression (anorexia). Contrastingly, increased AMP-activated protein kinase (AMPK) activity by ghrelin promotes appetite (orexia). However, the interplay between these mechanisms remains poorly defined. The relationship between the anorexigenic hormones, insulin and leptin, and the orexigenic hormone, ghrelin, on mTORC1 signalling was examined using S6 kinase phosphorylation as a marker for changes in mTORC1 activity in mouse hypothalamic GT1-7 cells. Additionally, the contribution of AMPK and mTORC1 signalling in relation to insulin-, leptin- and ghrelin-driven alterations to mouse hypothalamic agouti-related protein (AgRP) mRNA levels was examined. Insulin and leptin increase mTORC1 activity in a phosphoinositide-3-kinase (PI3K)- and protein kinase B (PKB)-dependent manner, compared to vehicle controls, whereas increasing AMPK activity inhibits mTORC1 activity and blocks the actions of the anorexigenic hormones. Ghrelin mediates an AMPK-dependent decrease in mTORC1 activity and increases hypothalamic AgRP mRNA levels, the latter effect being prevented by insulin in an mTORC1-dependent manner. In conclusion, mTORC1 acts as an integration node in hypothalamic neurons for hormone-derived PI3K and AMPK signalling and mediates at least part of the assimilated output of anorexigenic and orexigenic hormone actions in the hypothalamus

Luminance controlled pupil size affects Landolt C task performance

Subjects judged the orientation of a 2 min. gap Landolt C located at a distance of 2.4 m. The stimuli were presented in central vision on a CRT, at low to medium contrast. The effects of varying the spectrum and luminance of surround lighting were assessed on both pupil size (measured using infrared pupillometry during task performance) and task accuracy. The task display was protected from the surround lighting, so that its luminance and contrast could be varied independently of the changes in the surround lighting. Indirect surround illumination was provided by either two illuminants of very different scotopic spectral content but with the same photopic luminance (Experiments 1 and 3), or by using the same illuminant at two different luminance levels (Experiment 2). In Experiment 3, the effect of changing surround spectrum was compared to the effect of varying task background luminance between 12 cd/m[sup 2] and 73 cd/m[sup 2]. In all experiments, scotopically enhanced surround lighting produced pupil areas which were reduced by almost 50% in comparison with surround lighting with relatively less scotopic luminance. Concomitantly there was improvement in Landolt C task performance with the scotopically enhanced surround lighting at all contrast and luminance levels. In these experiments, smaller pupil sizes were associated with significantly better visual-task performance in spite of lower task retinal illuminance when compared to the condition with larger pupils. These results suggest that changes in surround spectrum can compensate for the effect on task performance of a reduction in task luminance and supports the hypothesis that lighting energy savings could accrue in the workplace by shifting lamp spectra to obtain greater scotopic efficacy