Circadian rhythms of metabolism

Contact: PD Dr. Olga Ramich

A number of metabolic processes and hormones show pronounced 24-hour rhythms. These rhythms are driven by so-called clock genes which “autonomously” control their own synthesis via linked cycles of up- and downregulation. Clock genes regulate different metabolic processes and could be in turn entrained by the light and food intake (Fig.1). The main aim of our project is to understand how the circadian clock affects metabolism in humans and which role they play in the metabolic response to the food intake.

Fig. 1: Circadian regulation of metabolism Circadian clock in mammals consists of the master clock in the suprachiasmatic nucleus (SCN) of hypothalamus which is synchronized by light/dark signals and the peripheral clock orchestrated by master clock and controlling metabolic rhythms. Food consumption can also entrain endogenous clock but has a more influence on peripheral clock then on the SCN (Kessler, Pivovarova-Ramich. Int J Mol Sci. 2019). Images: Adapted from Servier Medical Art by Servier (https://smart.servier.com/)

We have demonstrated diurnal oscillations of key genes of glucose, lipid and energy metabolism as well as inflammatory genes in human blood cells and adipose tissue. Moreover, we found that the expression of clock genes in human adipose tissue is regulated by body weight changes. Even isocaloric changes in carbohydrate and fat intake and the time of the food intake affect circadian rhythms in humans.

In our recent human study, we investigated whether the consumption of carbohydrates and fat at different times of the day induces different metabolic effects. This study showed that the time of carbohydrate and fat consumption can affects glycemic control in humans. Consumption of high carb meals in the evening induces an unfavorable effect on blood glucose level and glycemic control in subjects with impaired glucose metabolism.

 

Fig. 2: Diurnal variation in postprandial glucose response Postprandial glucose responses to the same test meals – high-carb (MTT-HC) or high-fat (MTT-HF) – in the morning at 9.00 a.m. and in the afternoon at 3.40 p.m. Filled bars show values in the morning and striped bars – values in the afternoon in subjects with normal glucose tolerance (blue) and impaired glucose metabolism (red). (Kessler et al. Sci Rep. 2017)

We further observed that levels of blood glucose, plasma lipidome, inflammatory markers, substrate oxidation, as well as postprandial hormone secretion was strongly dependent on the day time. Indeed, the postprandial glucose level in the afternoon was markedly higher than postprandial levels after the same meal in the morning which suggests a decrease in glucose tolerance as the day progresses. Notably, the afternoon decline in glucose tolerance was more pronounced in subjects with impaired glucose metabolism (Fig.2).

In summary, our data shows that both meal timing and food composition can alter circadian rhythms in humans and in this way affect dietary-induced metabolic response in humans. In the ongoing human study, we investigate effects of intermittent fasting on the glucose metabolism and other metabolic parameters in subjects with an increased diabetes risk.