Mouse physiques use glucose (carbohydrate) as it fuels energy when awake, active and switch to fat (lipid) when they are asleep. The team discovered that agitating this natural cycle may lead to diabetes but then again, amazingly, also can enhance exercise endurance. This discovery opens the option of choosing the right time to exercise for losing body fat but also raises the fear of using histone deacetylase 3, or HDAC3 inhibitors as nobbling drugs for endurance exercise. This study appears in Nature Medicine.
"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, assistant professor of medicine -- diabetes, endocrinology, and metabolism, and of molecular and cellular biology at Baylor. "The circadian clock works by turning certain genes on and off as the 24-hour cycle progresses. HDAC3 is a key connection between the circadian clock and gene expression. Our previous work showed that HDAC3 helps the liver alternate between producing glucose and producing lipid. In this work, we studied how HDAC3 controls the use of different fuels in skeletal muscle."
Skeletal and the voluntary muscles are vital in the control of blood glucose in our body. They consume most of the glucose in our body, and if they develop insulin and thus are not able to use glucose, then diabetes most likely develop. To study the role of HDAC3 in mouse skeletal muscle, Sun, and colleagues innately engineered lab mice to reduce HDAC3 only in the skeletal muscles. Then they compared these knocked-out mice with normal mice concerning how their muscles burn fuel.
Unexpected Results Shown On Test Subjects
When a mouse eats normally, their blood sugar surges and insulin is released, which kindles muscles to take in and use glucose as energy. "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 routine, they showed superior stamina, "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 a low performance in endurance exercises. That's the surprise."
Granting these studies were done in mice, the scientists take risks that human muscles most likely will follow the same results as the mice do. The study now opens more possibilities and promoting body fat burning by increasing workout activity. "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."
