Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats.

INTRODUCTION: With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular mechanisms in peripheral organs. The central timing system is sensitive to changes in the external environment such as those of the light-dark cycle, meal timing and meal composition. We investigated how changes in diet composition and meal timing would affect the daily hepatic expression rhythms of the nuclear receptors PXR and CAR and of enzymes involved in P450 mediated drug metabolism, as such changes could have consequences for the practice of chronotherapy. MATERIALS AND METHODS: Rats were subjected to either a regular chow or a free choice high-fat-high-sugar (fcHFHS) diet. These diets were provided ad libitum, or restricted to either the light phase or the dark phase. In a second experiment, rats had access to chow either ad libitum or in 6 meals equally distributed over 24 hours. RESULTS: Pxr, Alas1 and Por displayed significant day-night rhythms under ad libitum chow fed conditions, which for Pxr was disrupted under fcHFHS diet conditions. Although no daily rhythms were detected in expression of CAR, Cyp2b2 and Cyp3a2, the fcHFHS diet did affect basal expression of these genes. In chow fed rats, dark phase feeding induced a diurnal rhythm in Cyp2b2 expression while light phase feeding induced a diurnal rhythm in Car expression and completely shifted the peak expression of Pxr, Car, Cyp2b2, Alas1 and Por. The 6-meals-a-day feeding only abolished the Pxr rhythm but not the rhythms of the other genes. CONCLUSION: We conclude that although nuclear receptors and enzymes involved in the regulation of hepatic drug metabolism are sensitive to meal composition, changes in meal timing are mainly effectuated via changes in the molecular clock.

Effects of introspecting about reasons: inferring attitudes from accessible thoughts.

Previous research has shown that analyzing reasons can change people's attitudes, but the exact mechanisms of this effect have not been entirely clear. It was hypothesized that introspecting about reasons focuses people's attention on thoughts that are accessible in memory and increases the extent to which people view their accessible thoughts as applicable to their current attitudes. In Study 1, college students formed initial impressions of a target person, and then positive or negative thoughts about the target person were made memorable. After a delay, half of the participants analyzed reasons for their attitude and half recalled the target person's behaviors. As predicted, people who analyzed reasons reported attitudes toward the target person that were based more on what they could recall about her. Study 2 showed that this effect occurs regardless of whether people initially form an online impression. Implications for the effects of analyzing reasons and for attitude formation are discussed.

Knowing what you'll do: effects of analyzing reasons on self-prediction.

Analyzing the reasons why one would or would not act in a certain way was predicted to increase the perceived likelihood of the behavior and to lower the accuracy of the self-predictions. In 3 studies, college students predicted whether they would act in friendly or unfriendly ways toward an acquaintance. Those asked to analyze reasons why they would or would not perform the behaviors, as compared with no-analyze controls, were more likely to say they would perform the behaviors, showing a confirmation bias; made less accurate predictions, because analyzing reasons changed their predictions but not their actual behavior; and were more overconfident, because analyzing reasons lowered accuracy but not confidence. Each of these effects was especially pronounced when people's initial liking for the target person was different from the valence of the behavior they were predicting.