Disruption of Circadian Cycles Linked to Weight Gain

Every night during finals week, I studied into the wee hours of the morning and caught only a few hours of sleep. It was exhausting! After finals were over, I felt like a heavy weight had been lifted off my shoulders, but I also felt a few pounds heavier! Sure, late night studying was paired with late dinners and snacks, but the weight came so quickly and was incredibly difficult to lose. What happened? I blamed my overly self-conscious analysis and the high calorie foods. Now, researchers at Vanderbilt suggest another cause: disruption of the sleep-awake cycle!

It’s well known that nightshift workers and sleep-deprived people have a high risk of developing obesity and diabetes. This is because their bodily systems are forced to run against their intrinsic biological clocks. The disruption of normal light-dark cycles induces an aberrant metabolism. As we learned from Juan’s and Kate’s posts last year, the circadian system is governed by suprachiasmatic nuclei (SCN) in the hypothalamus, which orchestrates the clocks of internal organs and tissues according to light-dark cycles. In the February 2013 issue of Current Biology, researchers at Vanderbilt were the first to show definitively that insulin levels are also controlled by the body’s circadian clock.

Insulin regulates the body’s fat and carbohydrate metabolism. When you digest food, carbohydrates are broken down into the simple sugar glucose, which is absorbed into the blood stream. Too much glucose in the blood is toxic, so insulin stimulates the transfer of glucose into your liver, muscle, and fat cells to remove excess glucose from the blood. In this study, mice were shown to be more sensitive to insulin during the high activity, feeding phase. This means that they were better able to transfer glucose out of the blood and use it for energy during this active state. In contrast, mice were less sensitive to insulin during their inactive, fasting phase (sleep-state), which is termed insulin resistance. For this reason, glucose is primarily converted into fat during the inactive phase. This is why it is best to fast during your night cycle, between dinner and breakfast!

But what happens to insulin’s actions when the circadian clock is disrupted? To answer this question, the research team used Bmal1 knockout mice. When this clock gene is mutated, mice have impaired circadian behaviors and develop obesity. The researchers found that Bmal1 knockout mice were always in an insulin-resistant mode, similar to their inactive, fasting phase. Surprisingly, the researchers were able to bring insulin back to its normal circadian rhythm when they replenished the protein produced by the missing gene. In this way, the mice had reduced insulin resistance, so insulin’s actions were similar to wild-type mice, and they didn’t gain any excess weight!

To test whether disruptions in the sleep-awake cycle influenced body fat levels, wild-type mice were placed in a lit environment for three months, which completely disrupted their circadian cycles, and were fed a high-fat diet. Even though these mice ate less food than mice placed under a normal light-dark cycle, they gained more weight! It seemed that the mice were always in an inactive, fasting phase, so more glucose was converted into fat for storage instead of being burned for energy.

Taken together, these results suggest that to maintain a healthy lifestyle, we have to be conscious of what we eat, how much we eat, and when we eat! Since it is now definitive that insulin follows a rhythmic pattern that is sensitive to the activity state of our body, we should avoid late night snacks! So what should you do between dinner and breakfast? Sleep – at least until your biological clock goes off!

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References:

Shi S.Q., Ansari T.S., McGuinness O., Wasserman D. & Johnson C. (2013). Circadian Disruption Leads to Insulin Resistance and Obesity, Current Biology, DOI: 10.1016/j.cub.2013.01.048

Lamia K.A., Sachdeva U.M., DiTacchio L., Williams E.C., Alvarez J.G., Egan D.F., Vasquez D.S., Juguilon H., Panda S., Shaw R.J. & Thompson C.B. & (2009). AMPK Regulates the Circadian Clock by Cryptochrome Phosphorylation and Degradation, Science, 326 (5951) 437-440. DOI:10.1126/science.1172156

Images adapted from  Ocean/Corbis, Clkr and by Kate Jones and Jooyeun Lee.