When we think of circadian rhythm, we likely focus on the suprachiasmatic nucleus, i.e., the master biologic clock in our brains that aligns with light/dark cycles to mediate metabolism and influence sleep patterns. However, an article in the September 2018 issue of The Scientist discussed the biologic clock within skeletal muscle cells.
Muscle tissue stores up to 70% of a body’s sugar uptake. These muscle clocks impact the ability of muscle tissue to take up glucose in response to insulin and muscle contractions: “During an animal’s waking hours, feeding—which releases insulin from the pancreas—and physical activity induce the movement of the glucose transporter GLUT4 to the cell membrane. Studies show that disrupting clock genes in the muscle impairs the transcription of GLUT4 and other key genes involved in this process. Proteins required to metabolize sugars and lipids are also produced in a circadian manner. Researchers have found that genes that regulate the storage of these fuels reach peak expression levels when animals are preparing for rest, while those involved in breaking them down for energy production peak just before the active phase begins.”
Depending on an animal’s circadian cycle, the muscle clock regulates the type of fuel burned—when muscle is active during waking hours, it burns glucose; when the animal is asleep or at rest and fasting, muscle turns more to lipids and amino acids. Genes involved in metabolism are expressed at different times of the day based on the circadian rhythm. Researchers have found that the muscle’s intrinsic rhythms could be tweaked in mice by changing the timing of feeding, which is an important cue for other peripheral clocks. Scheduled exercise also tunes the muscle’s clocks, affecting the expression of circadian genes such as those involved in maintaining the muscles’ contractile properties. Alterations in tissue-specific timekeepers might influence sarcomere fiber length and contractility. There is the potential to alter the force generated by muscle, causing weakness and increasing susceptibility to injury.
There are other peripheral clocks in the body, including those in the liver, pancreas and adipose tissues. For example, a “clock” within the pancreas is responsible for maintaining proper secretion of insulin.
With this newly recognized construct of circadian rhythms and integrative tissue interaction throughout the body, it might be possible to use this information to help modulate insulin sensitivity, particularly in horses demonstrating insulin resistance and other endocrine aberrations.