Weight-Loss Surgery That Reprograms the Body’s Internal Clock to Improve Metabolism and Eating Behavior

Scientists studying gastric bypass surgery, a treatment for severe obesity that also ameliorates type 2 diabetes, discovered that, in mice, this surgery reprograms the biological day/night “clock” to adjust the timing and amount of food consumption and improve glucose (sugar) metabolism. In designing the study, they sought to explore a potential connection between weight- loss surgery and the body’s innate molecular clock based on previous research. Past studies showed that this clock synchronizes metabolism, eating, and other processes with 24-hour day/night cycles, and that risks for obesity and type 2 diabetes increase when day/night cycles are disrupted, for example, when people do shift work.

For their study, the researchers compared mice that had Roux-en-Y gastric bypass (RYGB) surgery to those of similar body weight that did not have the surgery, with both groups on a high-fat diet. While a high-fat diet typically alters the amount and timing of food intake in mice, those that had RYGB surgery ate less overall and shifted more of their food consumption to the time in the day/night cycle when mice normally eat. The researchers then analyzed different tissues for potential effects on genes encoding clock functions, which exist throughout the body, and found that RYGB surgery led to changes in the activity of clock genes in the liver, an organ with important roles in glucose metabolism. To further test the relevance of the clock to surgical outcomes, they examined mice that lacked a key clock gene. They discovered that, compared to other mice, the clock-deficient mice lost less weight after RYGB surgery and did not have improvements in glucose metabolism. Thus, a functional clock was needed for these beneficial effects.

This study in mice demonstrates the role of the body’s molecular clock in weight loss, eating times, and glucose metabolism after RYGB surgery for obesity. If the molecular clock has a similar role in RYGB surgical outcomes in humans, researchers could study whether adjusting meal and snack times may yield more health benefits. Further research on the effects of different bariatric (weight loss) surgical procedures could also lead to new, less invasive treatment approaches.