The rhythm of feeding Effect of nutrients on metabolism and the molecular clock

This thesis describes studies we performed to assess the relationship between nutrients and the circadian clock. We assessed the effects of sugar and fatty acids on the daily rhythmicity of hepatic clock genes and whole-body metabolism in vivo, and on circadian rhythmicity of clock genes in vitro. First, we show in rats that light-phase sugar intake increases food efficiency and body weight compared to light-phase fat intake. Thus, timing of specific macronutrients can affect food efficiency, most likely due to a shifted oxidation pattern. Second, we show an interaction effect of diet timing and composition on hepatic steatosis: consuming a high fat, high sugar diet during the rat’s inactive period resulted in more hepatic fat than consuming the same diet during the dark (active) period. Possibly because the HFHS-light fed animals did not shift their energy expenditure pattern with the shifted time of food intake, resulting in an imbalance between energy intake and expenditure. Next, we investigated in hypothalamic neuronal cells the direct effects of sugar and fat (palmitate) on clock gene rhythms. Palmitate altered the expression profile of the clock gene Bmal1, and sugar altered the expression profile of the clock gene Per2. Taken together, this thesis shows that both fat and sugar affect the hypothalamic clock in a direct manner, independent of caloric content. Furthermore, there is a complementary effect of diet timing and composition on whole-body metabolism and peripheral clock gene expression. These results are important for increasing our understanding of the unhealthy effects of shift work.