Beware! Making muscles burn more fat and less glucose can increase exercise endurance, but could simultaneously cause diabetes, warns a new study.
The findings, published in the journal Nature Medicine, indicated that skeletal muscles, the voluntary muscles, are important in the control of blood glucose in the body.
They consume most of the glucose and if they develop insulin resistance and consequently are not able to use glucose, then diabetes likely will develop.
Mouse muscles use glucose (carbohydrate) as fuel when the animals are awake and active and switch to fat (lipid) when they are asleep. The team discovered that disrupting this natural cycle may lead to diabetes but, surprisingly, also can enhance exercise endurance.
“How the muscle uses glucose is regulated by its internal circadian clock that anticipates the level of its activity during the day and at night,” said senior author Dr. Zheng Sun from Baylor College of Medicine.
“In this work, we studied how HDAC3 controls the use of different fuels in skeletal muscle,” Sun added.
The switch is controlled by a molecule called histone deacetylase 3 (HDAC3). This finding opens the possibility of selecting the right time to exercise for losing body fat but also raises the concern of using HDAC inhibitors as doping drugs for endurance exercise.
To study the role of HDAC3 in mouse skeletal muscle, scientists genetically engineered laboratory mice to deplete HDAC3 only in the skeletal muscles.
Then they compared these knocked out mice with normal mice regarding how their muscles burn fuel.
When normal mice eat, their blood sugar increases and insulin is released, which stimulates muscles to take in and use glucose as fuel.
“When the knocked out mice ate, their blood sugar increased and insulin was released just fine, but their muscles refused to take in and use glucose,” said Sun. “Lacking HDAC3 made the mice insulin resistant and more prone to develop diabetes.”
Yet, when the HDAC3-knocked out mice ran on a treadmill, they showed superior endurance, “which was intriguing because diabetes is usually associated with poor muscle performance,” said Sun. “Glucose is the main fuel of muscle, so if a condition limits the use of glucose, the expectation is low performance in endurance exercises. That’s the surprise.”
The study opens the possibility of promoting body fat burning by increasing exercise activity during the periods in which muscles use lipid, which is at night for people.
“Losing body fat would be easier by exercising lightly and fasting at night,” said Sun. “It’s not a bad idea to take a walk after dinner.
ANI