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Researchers supported by the Swiss National Science Foundation (SNSF) have discovered a biological clock in our muscle cells. It could be involved in regulating metabolism and the development of diabetes.
Biological clocks tick everywhere in our body. They release the hormone melatonin during sleep, promote the secretion of digestive enzymes after lunch and keep us awake during the day. A master clock in the brain synchronizes all other clocks in the different organs. Researchers supported by the Swiss National Science Foundation (SNSF) have discovered that such a “circadian clock” ticks in our muscle cells. If this clock is out of rhythm, this could have a decisive influence on the development of type 2 diabetes. The scientific work of the research team was recently 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 over time of the day varies, and depending on the time of day, one lipid is sometimes more dominant than another. Could this be related to the influence of the biological clock? The international team tested this hypothesis by examining volunteers. To this end, the participants' main clock was synchronized: Before the study began, they had to adhere to a regular daily schedule with regard to meals and light exposure. A small muscle sample was taken from the thigh every four hours to analyze the lipid composition.
The research team found a clear correlation between the lipid composition and the time of day, explains Howard Riezman, who led the study together with his colleague Charna Dibner in Geneva. "Since the lipid composition fluctuated widely within the test group, we needed further evidence to support this thesis," Riezman continues.
In a second step, the researchers switched to an in vitro experiment. They grew human muscle cells and synchronized them artificially, without a master clock, using a signaling molecule that is normally secreted by the body. A periodic fluctuation in the cellular lipid composition was observed, similar to the experiments carried out on humans. However, if the researchers interrupted the clock mechanism by inhibiting the relevant genes, the periodic lipid fluctuations largely disappeared.
Diabetes and sleep disorders are related
"We were able to clearly demonstrate that this fluctuation in the lipid composition in our muscles depends on our circadian rhythm," explains lead author Ursula Loizides-Mangold. "But the most important question remains: What is the significance of this mechanism?" Riezman is of the opinion that the biological clock in the muscle could regulate the insulin sensitivity of the muscle cells through its action on the lipids. Because lipids are part of the cell membrane, they affect the ability of the molecules to enter and exit the muscle cells. A change in the membrane composition could influence the response of the muscle to the hormone and its ability to absorb blood sugar.
A low insulin sensitivity of the muscle leads to a so-called insulin resistance, a known cause of type 2 diabetes. “According to studies, there is a connection between circadian clocks, insulin resistance and the development of diabetes,” explains Charna Dibner, co-leader of the study. “If we can establish a link between the circadian mechanism and type 2 diabetes through lipid metabolism, it could have significant therapeutic implications. Thanks to our new possibilities for in-vitro examination of cell clocks in human muscles, we can test 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