New study muscles measure the respective time of day
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Biological clocks are everywhere in our bodies. They release the hormone melatonin while they sleep, favor the secretion of digestive enzymes after lunch and keep us awake during the day. A master clock in the brain synchronizes all the other clocks in the various organs. Researchers supported by the Swiss National Science Foundation (SNSF) have discovered that such a "circadian clock" is ticking in our muscle cells. If this clock gets out of hand, this could decisively influence the development of type 2 diabetes. The scientific work of the research team has recently been published in the journal PNAS (*).
Removal of muscle tissue spread throughout the day
Researchers from the University of Geneva, the University of Bath, the Université Claude Bernard in Lyon, the EPFL, the University of Surrey and the Nestlé Institute of Health Sciences found that the composition of different types of fats (lipids) in our muscle cells in the course Depending on the time of day, sometimes one lipid is more dominant than another. Could this be related to the influence of the biological clock? The international team has tested this hypothesis by conducting a voluntary volunteer study. For this purpose, the participants' master clock was synchronized: they had to adhere to a regular daily routine with regard to meals and light exposure before starting the study. Every four hours, a small muscle tissue specimen was taken from the thigh to analyze the lipid composition.
The research team identified a clear correlation between lipid composition and time of day, explains Howard Riezman, who led the study with his colleague Charna Dibner in Geneva. "Because the lipid composition within the subject group fluctuated greatly, we needed further evidence to substantiate this thesis," Riezman continues.
In a second step, the researchers therefore switched to an in vitro experiment. They bred human muscle cells and synchronized them artificially, without a master clock, using a signaling molecule that is normally secreted by the body. A periodic variation of the cellular lipid composition was observed, similar to the human experiments. However, when researchers disrupted the clock mechanism by inhibiting the relevant genes, the periodic lipid fluctuations largely disappeared.
Diabetes and sleep disorders are related
"We clearly demonstrated that this variation in lipid composition in our muscles depends on our circadian rhythm," says lead author Ursula Loizides-Mangold. "But the key question remains: what is the significance of this mechanism?" Riezman believes that the biological clock in the muscle, through its action on the lipids, could regulate the insulin sensitivity of muscle cells. Because lipids are part of the cell membrane, they affect the ability of molecules to enter and exit the muscle cells. Changing the membrane composition could affect muscle response to the hormone and its ability to absorb blood sugar.
Low insulin sensitivity in the muscle leads to what is known as insulin resistance, a known cause of type 2 diabetes. "Studies have found a link between circadian clocks, insulin resistance, and the development of diabetes," explains Charna Dibner, co-lead investigator. "If we can show a link between the circadian mechanism and type 2 diabetes based on lipid metabolism, this could have significant therapeutic implications. Thanks to our new capabilities of in vitro cell-clocking in human muscle, we can validate this hypothesis in our next study. "
(*) U. Loizides-Mangold et al .: Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro. PNAS (2017). DOI: 10.1073 / pnas.1705821114