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Burning More Fat and Less Glucose = Increased Chance of Diabetes

Posted on Jan. 4, 2017, 6 a.m. in Diabetes Exercise

Prompting muscles to burn more fat and less glucose can increase exercise endurance, but may also simultaneously cause diabetes.

Researchers from Baylor College of Medicine recently discovered that disrupting the day-night cycle of lab mice made their muscles burn more fat and less glucose. This mouse model showed increased physical endurance, but because less glucose was burned, scientists speculate that this could lead to diabetes. Muscles use glucose as fuel when we are awake and active, but when we are asleep the muscles switch over to burning fat. This switch is controlled by a molecule called HDAC3 and opens a new concern in exploiting this effect in doping drugs that could inhibit this molecule. However, this finding published in the Nature Medicine does offer a new hope for people wanting to lose weight.

Coaxing Muscles to Burn Fats Efficiently

Our internal circadian clock regulates how our muscles use glucose and also turns certain genes on or off during the 24-hour cycle. The molecule HDAC3 is closely linked with this internal clock and helps our liver decide when to produce glucose or fats. Our skeletal muscles consume most of the blood glucose in our bodies. However, if our muscles are not able to burn enough glucose, they become insulin resistant, making our bodies prone to developing diabetes.

In the experiment on mice, researchers wanted to understand the role of HDAC3 in the muscles. The mice were genetically engineered to have a depleted level of HDAC3. After being fed food, the muscles refused to burn glucose making the mice insulin resistant and more prone to diabetes. Surprisingly, when the mice were put on treadmills, they showed enhanced levels of muscle endurance. Usually, diabetes is associated with a decrease in muscle performance.

When researchers studied what fueled the muscle endurance in the mice, they found that the muscles were breaking down amino acids which made the muscles switch to burning fats very efficiently. The body carries more energy from fats than from glucose and researchers say that tricking the muscles to burn fat could increase endurance during low-intensity workouts. This is a bit of a departure from the traditional strategies of eating foods high in carbohydrates before exercising. However, concerns are being raised over the possibility of athletes using HDAC inhibitor drugs to fuel performance levels. Currently, there are drugs being tested using HDAC inhibitors to treat several diseases.

Exercise in the Evening - Fast at Night

In the studies on mice, when normal mice are awake, the internal circadian clock expects a feeding cycle using HDAC3 to make the muscles burn more carbohydrates or glucose. When normal mice are sleeping, the clock expects a fasting cycle and expels the HDAC3 making the muscles burn fats. The study concludes that there is a link between the body's circadian clock and the molecule HDAC3.

Although these experiments have only been done on mice, the researchers are confident that human muscles will respond the same way. It's expected that the human body can be induced into burning more fat when exercising during the evening periods. To lose weight using this method, the recommendation is to do light exercise in the evening and fast all night.

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Sungguan Hong, Wenjun Zhou, Bin Fang, Wenyun Lu, Emanuele Loro, Manashree Damle, Guolian Ding, Jennifer Jager, Sisi Zhang, Yuxiang Zhang, Dan Feng, Qingwei Chu, Brian D Dill, Henrik Molina, Tejvir S Khurana, Joshua D Rabinowitz, Mitchell A Lazar, Zheng Sun. Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion. Nature Medicine, 2016; DOI: 10.1038/nm.4245

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