Daily Scheduled High Fat Meals Moderately Entrain Behavioral Anticipatory Activity, Body Temperature, and Hypothalamic c-Fos Activation

When fed in restricted amounts, rodents show robust activity in the hours preceding expected meal delivery. This process, termed food anticipatory activity (FAA), is independent of the light-entrained clock, the suprachiasmatic nucleus, yet beyond this basic observation there is little agreement on the neuronal underpinnings of FAA. One complication in studying FAA using a calorie restriction model is that much of the brain is activated in response to this strong hunger signal. Thus, daily timed access to palatable meals in the presence of continuous access to standard chow has been employed as a model to study FAA in rats. In order to exploit the extensive genetic resources available in the murine system we extended this model to mice, which will anticipate rodent high fat diet but not chocolate or other sweet daily meals (Hsu, Patton, Mistlberger, and Steele; 2010, PLoS ONE e12903). In this study we test additional fatty meals, including peanut butter and cheese, both of which induced modest FAA. Measurement of core body temperature revealed a moderate preprandial increase in temperature in mice fed high fat diet but entrainment due to handling complicated interpretation of these results. Finally, we examined activation patterns of neurons by immunostaining for the immediate early gene c-Fos and observed a modest amount of entrainment of gene expression in the hypothalamus of mice fed a daily fatty palatable meal

Food anticipatory activity on a calorie-restricted diet is independent of Sirt1

A number of studies have demonstrated that the Sirtuin family member, Sirt1, is a key integrator of growth, metabolism, and lifespan. Sirt1 directly interacts with and deacetylates key regulators of the circadian clock, positioning it to be an important link between feeding and circadian rhythms. In fact, one study suggests that Sirt1 is necessary for behavioral anticipation of limited daily food availability, a circadian process termed food anticipatory activity (FAA). In their study, mice overexpressing Sirt1 had enhanced FAA, while mice lacking Sirt1 had little to no FAA. Based on the supposition that Sirt1 was indeed required for FAA, we sought to use Sirt1 deletion to map the neural circuitry responsible for FAA. We began by inactivating Sirt1 using the cell-type specific Cre-driver lines proopiomelanocortin, but after observing no effect on body weight loss or FAA we then moved on to more broadly neuronal Cre drivers Ca2+/calmodulin-dependent protein kinase II and nestin. As neither of these neuronal deletions of Sirt1 had impaired FAA, we then tested 1) a broad postnatal tamoxifen-inducible deletion, 2) a complete, developmental knockout of Sirt1, and 3) a gene replacement, catalytically inactive, form of Sirt1; but all of these mice had FAA similar to controls. Therefore, our findings suggest that FAA is completely independent of Sirt1

Nutrient Sensor in the Brain Directs the Action of the Brain-Gut Axis in Drosophila

Animals can detect and consume nutritive sugars without the influence of taste. However, the identity of the taste-independent nutrient sensor and the mechanism by which animals respond to the nutritional value of sugar are unclear. Here, we report that six neurosecretory cells in the Drosophila brain that produce Diuretic hormone 44 (Dh44), a homolog of the mammalian corticotropin-releasing hormone (CRH), were specifically activated by nutritive sugars. Flies in which the activity of these neurons or the expression of Dh44 was disrupted failed to select nutritive sugars. Manipulation of the function of Dh44 receptors had a similar effect. Notably, artificial activation of Dh44 receptor-1 neurons resulted in proboscis extensions and frequent episodes of excretion. Conversely, reduced Dh44 activity led to decreased excretion. Together, these actions facilitate ingestion and digestion of nutritive foods. We propose that the Dh44 system directs the detection and consumption of nutritive sugars through a positive feedback loop

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

Pediculosis capitis: Treatment options among schoolchildren in Greece

Background: Pediculosis capitis remains a significant health problem worldwide. Purpose: It was to record the preferred treatment options against pediculosis capitis in school-age children in Greece. Method and Material: A randomly selected, stratified sample of schools from all over Greece was used. A questionnaire with closed and open-type questions was used. Five thousand, eighty four questionnaires were distributed and 2792 returned. Descriptive statistics was conducted. Results: Median age of the children was 8 (3-13) years. 88,6% of the parents answered the would not visit a dermatologist in the case of pediculosis. Insecticides were the treatment of choice in most cases (80 %), while louse comb as a single treatment was preferred by 1 % of the parents. Conclusion: Drugs remain the main treatment choice in Greece. Dermatologists infrequently treat patients with pediculosis capitis

Calorie restriction of leptin knockout mice.

<p>Measure of fraction of time engaged in activity during the anticipatory period prior to feeding (ZT 7–9). Beginning from day 7, WT AL and WT CR mice have statistically significant differences in fraction of time spent engaging in (A) total high activity behaviors (sum of hang, jump rear, and walk) as well as individual behaviors such as (C) hang, (E), jump, (G) rear, and (I) walk. In contrast, Leptin KO mice on AL and CR feeding have no statistical difference in (B) total high activity behaviors. (D) Hang reaches statistical significance at day 14 that is sustained through day 28 and (F) jump reaches transient statistical difference at day 14 and 28. (H) Rear and (J) walk is not statistically different between AL and CR. Statistics were performed using the Mann-Whitney Test with post-test, *  =  p<0.05; **  =  p<0.01; and ***  =  p<0.001. Error bars represent IQR. n = 8 WT AL; n = 8 WT CR; n = 7 KO AL and n = 8 KO CR.</p

Daily palatable meals of rodent high fat diet do not cause a pre-prandial increase in activity in 129S1 mice, which do show robust food anticipatory activity for 60% CR (Experiment

<p> <b>3).</b> Fraction of time per hour spent walking, hanging, jumping, or rearing observed in PM-fed 129S1 mice during each hour of the 24-hour recording in Days 0, 7, and 14 (A–C). Free-feeding mice fed high fat diet at ZT 9 do not show any significant differences in pre-prandial high activity after 14 days in feeding schedule. Fraction of time per hour spent walking, hanging, jumping, or rearing observed in 129S1 mice in 60% CR schedule during each hour of the 24-hour recording in Days 14 and 21 (D–E). Mice subject to calorie restriction show significantly higher pre-prandial high activity in Days 14 and 21. Lines represent medians +/− IQ Range (significance was tested with Mann-Whitney test with Dunn’s post test. * denotes p<0.05.</p

Body temperature is moderately correlated with Food Anticipatory Activity.

<p>(A) Mean temperature during the 2.5 h preceding PM presentation. Error bars represent SEM. Statistical comparisons were performed using an ANOVA followed by Tukey-Kramer multiple comparisons test, * denotes p<0.05, ** denotes p<0.01, and *** denotes p<0.001. (B) Mean temperature and high activity 14 days after start of PM feeding regimen. Mean temperature is represented by dashed lines in top half of the panel (corresponding to left y-axis) and mean high activity in seconds is represented by the solid line in the bottom half of the panel (corresponding to right y-axis). Temperature plotted against the fraction of high activity during the 2.5 H preceding mealtime for day 0 (C), day 7 (D), day 14 (E), and Day 21 (F). Linear regression lines and R² are shown.</p

Calorie restriction and baseline home cage behavior of leptin knockout mice.

<p>(A) Leptin KO and WT mice on AL feeding conditions gain weight while Leptin KO and WT mice on CR lose weight. (B) Leptin KO mice on AL and CR feeding conditions have similar percent gain and loss of weight relative to percent changes in weight of WT controls on AL and CR feeding conditions. Leptin KO mice on CR are more resistant to weight loss (p<0.01 for Leptin KO CR vs. WT CR). (C) High activity behaviors of WT mice are much higher than Leptin KO mice. WT and Leptin KO mice have comparable (D) food bin entry on AL feeding. WT mice (E) hang, (F) jump, (G) rear and (H) walk more than Leptin KO mice. Statistics were performed using the Mann-Whitney Test *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001. Error bars represent IQR for behavioral data and SEM for body weight data. n = 16 WT AL and n = 15 KO AL.</p