Burning more fat and less glucose could lead to diabetes

Making muscles burn more fat and less glucose can increase exercise endurance, but could simultaneously cause diabetes, says a team of scientists from Baylor College of Medicine and other institutions.

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.

The switch is controlled by a molecule called histone deacetylase 3, or HDAC3. 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,

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.

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.

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 HDAC3-knocked out mice ran on a treadmill, they showed superior endurance, their muscles break down more amino acids. This changed the muscles’ preference from glucose to lipids and allowed them to burn lipid very efficiently. This explains the high endurance, because the body carries a much larger energy reservoir in the form of lipid than carbohydrate.

The finding challenges the widely-used carbohydrate-loading (carbo-loading) strategy for improving endurance performance. “Carbo-loading didn’t make evolutionary sense before the invention of agriculture,”

In normal mice, when the mouse is awake, the clock in the muscle anticipates a feeding cycle and uses HDAC3 to turn off many metabolic genes. This leads the muscles to use more carbohydrate,” said Sun. “When the animal is about to go to sleep and anticipates a fasting cycle, the clock removes HDAC3. This leads the muscles to use more lipid.

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.”

— source bcm.edu

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