Disrupted circadian rhythm may not help achieve maximum weight loss after bariatric surgery

A newly released basic science study of Roux-en-Y gastric bypass (RYGB) suggests that a functioning circadian clock, or sleeping at night and being awake during the day, can help patients achieve a higher amount of weight loss following the surgery. The study conducted in a mouse model is one of the first to shed light on how researchers and clinicians might continue to improve the outcomes following RYGB by correcting disruptions to the circadian clock. The findings were unveiled during a poster presentation at The Obesity Society Annual Meeting at ObesityWeekSM 2016 in New Orleans, Louisiana.

Prior research observations suggest that appropriate timing of calorie consumption and minimal disruption of the light/dark cycle set by the environment are crucial for a healthy energy balance and metabolism. However, little is known about the potential role of this molecular clock on maximizing the beneficial metabolic effects of bariatric surgery - one of the most effective therapies available for obesity.

"Our findings from this mouse study suggest that patients with a disrupted circadian rhythm - such as night-shift workers and those with night-eating syndrome - may not be able to achieve the maximum amount of weight loss resulting from bariatric surgery," said the study's lead researcher Mohamad A. Mokadem, MD, ABOM, of the University of Iowa. "Our research shows that it could be important for patients to have a normal circadian clock pre-surgery to maximize weight loss following surgery."

The research implications for patients are drawn from a study conducted in mice, which is one of the first steps toward designing and replicating such a study in humans. Study authors say that more research is needed to better understand the role of circadian rhythm regulators or "clock genes" in the reversal of obesity, including research conducted in a patient population.

"Bariatric surgery has long been recognized as one of the most effective treatments for severe obesity," said Samer Mattar, MD, spokesperson for The Obesity Society and Professor of Surgery at Oregon Health and Science University. "This study is a step toward better understanding the underlying mechanisms affecting bariatric surgery outcomes, enabling us to continue to improve upon this form of treatment."

The Obesity Society reinforces that while bariatric surgery comes with risks, as does any surgery, it is a good option for some - but not all - patients.

"There are many options for patients with obesity from surgery to FDA-approved medications and weight-loss counseling," continued Dr. Mattar. "Patients with obesity should discuss their best options with a qualified obesity treatment specialist."

Abstract
Roux-en-Y gastric bypass reverses the high fat diet-induced disruption in circadian rhythmicity in mice

Background
Roux-en-Y gastric bypass (RYGB) is one of the most common and effective bariatric procedures performed in the US. We developed a mouse model of RYGB that recapitulates weight loss and diabetes improvement observed in humans after surgery. The RYGB model was previously used to demonstrate that metabolic improvements after surgery are due to a neuro-hormonal mechanism communicating energy signals between the gut and the brain. Disruption of circadian rhythmicity in humans (as in people with shift-work disorder) has been associated with obesity and insulin resistance and the efficacy of bariatric surgery may be attenuated in these subjects. Similarly, disruption of the molecular clock rhythmicity in mice induces insulin resistance and exacerbates obesity. What remains unknown is the role of circadian rhythm regulators or clock genes in the reversal of obesity such as in bariatric surgery.

Methods
We wanted to examine if bariatric surgery affects circadian rhythm regulators and behavior in diet-induced obesity (DIO).

Results
We found that high-fat diet (HFD) alters the circadian pattern of food intake by increasing calorie consumption during the light cycle from 21% to 40% of the daily total calorie intake. Interestingly, RYGB reverses this HFD-induced disruption in circadian feeding behavior by restoring the pattern of dark cycle food consumption to that of age-matched lean controls on regular chow diet (Figure 1). We also show that sham-treated obese mice pair fed to the RYGB group, during the dark cycle only, lose weight and improve their insulin sensitivity relative to their ad-libitum-fed counterparts (Figure 2). In addition, we found that DIO disrupts the expression of several clock genes (such as bmal1 and period 2 in the liver and period 1 in the small inestines) while RYGB seems to reverse or attenuate these changes (Figure 3).

Conclusions
RYGB reverses the HFD-induced disruption in circadian rhythm feeding behavior and clock gene expression. Further work is being formulated to evaluate the requirement of the molecular clock in the mechanism of energy and glucose regulation after RYGB. Being able to identify key molecules and pathways along the gut-brain axis that are involved in energy regulation after RYGB, can facilitate future development of less-invasive therapies for obesity and diabetes.