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Atlas of Circadian Metabolism

As part of a large-scale study, researchers constructed 24-hour metabolic profiles of mouse tissues and organs under conditions of energy balance and high-fat diet. Their findings provide an overview of how the various metabolic pathways in the body are interconnected and also reveal suitable time frames for anti-obesity therapies. The study was conducted under the aegis of the Helmholtz Zentrum München and the University of California Irvine in collaboration with the German Center for Diabetes Research (DZD). The results have now been published in 'Cell'.

Immunofluorescence of muscle fiber types. Source: Kenneth Dyar

The scientists generated 24 hour metabolic profiles of eight different tissues simultaneously. These included the suprachiasmatic nucleus in the hypothalamus (regarded as the principal circadian pacemaker in mammals), in addition to prefrontal cortex, skeletal muscle, liver, brown and white adipose tissue, blood and sperm.

To understand how diet impacts tissue synchronization and 24 hour metabolism the scientists compared all this data under normal and high-fat diets. High-fat food is known to disrupt circadian rhythms and cause metabolic diseases like obesity and diabetes. This temporal view of tissue metabolism enabled a better insight into how metabolism is changed in metabolic diseases, for example, in the case of obesity and diabetes.

Excess calories from fat upset metabolic rhythms
The researchers were also able to observe how high-fat food consumption disrupts tissue metabolism. In muscle tissue, for instance, they noticed that energy generation from fat and sugar occurred separately and in a very orderly sequence under conditions of energy balance. Under high fat diet, this typical pattern broke down completely and fat metabolism dominated. These changes have major implications for how diet can contribute to development of muscle insulin resistance.

Overall, the study provides an overview of the metabolic processes taking place in the respective tissue at any given time, and also reveals previously unknown links. From that, the authors say, one can also deduce the most promising time frames for administering metabolically effective medication.

Original publication:
Dyar, KA. et al. (2018): Atlas of Circadian Metabolism Reveals System-wide Coordination and Communication between Clocks. Cell, DOI: 10.1016/j.cell.2018.08.042