Daily rhythms in muscle mitochondria Effects of time-restricted feeding and exercise

The incidence of type 2 diabetes mellitus (T2DM) is reaching pandemic proportions with an estimated 500 million diabetics worldwide. The main risk factors for developing T2DM are excessive caloric intake as well as physical inactivity, but other behavioral risk factors such as performing shift-work have also been found to contribute to disease development. As our society increasingly relies on shift-work it is crucial to develop strategies that minimize these harmful effects. It is currently unknown what the mechanisms are behind the increased risk of shift-workers for metabolic disease. There is a possible role for erratic eating patterns as shift-workers often eat during the night, which is the inactive period of humans. Additionally, shift-workers are likely at an increased risk of having disturbed sleep/wake cycles and disturbed biological clocks in general, possibly leading to the development of metabolic disorders including T2DM.
Using the animal model of time-restricted feeding we confirm the close relationship between the biological clock, timing in eating behavior, diet composition and energy metabolism at the systemic (whole body), cellular and organellar level. More specifically, we conclude that the biological clock controls mitochondrial metabolism in skeletal muscle. In addition, disturbing or strengthening the biological clock affects both mitochondrial metabolism in skeletal muscle as well as systemic insulin sensitivity. The diverse range of metabolic disturbances that we found in our animal model of shift-work supports the idea of internal desynchronization of peripheral clocks and thereby disturbed metabolism as the underlying course of the increased risk for metabolic disorders in shift-workers.