Researchers have found that making muscles burn more fat but less glucose (carbohydrates) can lead to a boost in endurance. However, it can also cause diabetes.

For a study published in the journal Nature Medicine, researchers used mouse models to show that disrupting the natural cycle of glucose being used as fuel during the day - when the animals are active - could enhance exercise endurance but at the same time promote diabetes development.

According to Zheng Sun and colleagues, the molecule histone deacetylase 3 (HDAC3) is responsible for controlling the switch. This finding suggests the possibility that engaging in exercise at the right time will aid in losing body fat. However, there is also the concern that people may turn to HDAC inhibitors as potential doping drugs to get full benefit from endurance exercise.

Circadian Rhythm And Muscle Use

"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 Sun, the study's senior author.

He explained that the body's circadian clock functions by turning on and off certain genes within a 24-hour cycle, with HDAC3 being a key component between gene expression and the circadian clock. Earlier, the researchers were able to show that the molecule aids the liver in alternating the production of lipids and glucose. In this study, they focused on how HDAC3 is able to control fuel use in skeletal muscles.

Skeletal muscles are crucial in controlling blood glucose. These voluntary muscles use a lot of glucose, so if insulin resistance develops and the muscles fail to use glucose, diabetes is highly likely to develop.

Unexpected Results

The researchers depleted HDAC3 in the skeletal muscles of mice and, as expected, saw that the mice became insulin-resistant and developed higher chances of developing diabetes. But when the same mice were placed on treadmills, they exhibited superior endurance.

This is surprising for the researchers because diabetes is generally associated with low muscle performance. Glucose, after all, is the primary source of fuel for muscles. If glucose use was to be limited then, low endurance would ensue. However, this was not the case with the study.

When the researchers further studied the mice, they discovered that the spike in endurance the animals exhibited was due to skeletal muscles breaking down more amino acids. This led to a change in fuel preference for the muscles, going from glucose to lipids and allowing for fat to be burned more efficiently. Bodies have larger energy reserves in the form of lipids than glucose, so efficient lipid use paved the way for optimum endurance.

The study challenges the common notion that loading up on carbohydrates is the key to improving endurance.

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