Written by Tatjana Djakovic, Staff Writer. Caloric restriction in mice resulted in weight loss, but the weight was regained shortly.

Over the past three decades, obesity has increased at an alarming rate in the United States. Currently, 66% of adults are overweight or obese and by 2015, 75% of adults will be overweight or obese (1).  In an attempt to lose weight, people turn to dieting which can lead to weight cycling also known as “yo-yo” dieting.  Very-low calorie diets have the proven ability to achieve rapid weight loss but do not counteract the body’s natural tendency to return to its pre-diet weight (2). The elevated weight regain increases the risk for diabetes and related metabolic diseases. Scientists suspect that “yo-yo” effect reprograms the regions of the brain that release stress hormones which promote increased consumption of calorically dense foods resulting in an increased risk for greater weight gain and later obesity.  In addition, stress plays an important role in increasing behavior of rewarding substances, including calorically dense foods.

The current animal study was conducted to test the hypothesis whether previous experience with restricting the amount of calories consumed would produce changes in the regions of the brain dealing with stress which would lead to a tendency to over-consume high fat food. To examine the hypothesis, the scientists compared physiological and behavioral stress responses in mice after reducing the weight of the mice by 10-15%, which is typical of human weight loss during dieting (3).

The researchers measured how the mice responded to stress after being subjected to caloric restriction after 19 days. A tail suspension test was administered in which mice were hung by the tail briefly and their immobility was measured. From time spent immobile, there was a significant effect. It  indicated depression when the calorically restricted group spent approximately 40% more time immobile than controls (p<0.01). They also measured the levels of corticosterone (a hormone produced in the body), that serves as an indicator of the amount of stress. Calorically restricted mice had significantly increased stress response p<0.001) and approximately 72% higher corticosterone levels (p<0.05) after 15 minutes of exposure.  This group also had a delayed recovery at 45 min (p<0.001) and 75 minutes (p=0.05) (4).

The researchers determined the potential impact of reprogramming the brain, that occurs as a result of previous caloric restriction. It resulted in bingeing on a high fat diet during chronic stress.  After three weeks of caloric restriction, mice were given full access to their normal food until the restricted group reached the same weight as the controls. The mice were exposed to stressors such as: noise, predator smell and damp bedding overnight.  During the stressors, the mice that had undergone previous caloric restriction, consumed significantly more calories than control mice over the 10 days of testing (p<0.05).  The percentage of calories were significantly greater for calorically restricted mice compared with the controls (p<0.05). In addition, the previous restriction increased high-fat binge eating after three days of limited access (p<0.001) (4).

The researchers also analyzed the genetic component of how the mice were impacted by caloric restriction.  Corticotropin-releasing factor (CRF) was analyzed which promotes increased consumption of calorically dense foods.  CRF in the neurons of a specific region of the brain was significantly reduced, suggesting possible changes in the genetic response to caloric restriction.  The changes did not return to their previous state when the mice were returned to their normal diet (4).

These results reveal; reprogramming in regions of the brain involved in regulating stress response and appetite stimulation is driven by caloric restriction experience. In humans, changes would be expected to reduce weight by promoting behaviors to manage stress during dieting. This will benefit long term healthy weight maintenance.

Source: Pankevich, Diana E., et al. “Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating.” Journal of Neuroscience 30.48 (2010): 16399-16407.

© 2010 the authors

Posted June 27, 2013.

References:

  1. Wang, Y., & Beydoun, M. A.. The obesity epidemic in the United States—gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. (2007) Epidemiologic reviews, 29(1), 6-28.
  2. Prentice, Andrew M., et al. “Effects of weight cycling on body composition.” The American journal of clinical nutrition 56.1 (1992): 209S-216S.
  3. Redman LM, et al., Effect of calorie restriction with or without exercise on body composition and fat distribution. J Clin Endocrinol Metab. (2007) 92:865-872.
  4. Pankevich, Diana E., et al. “Caloric restriction experience reprograms stress and orexigenic pathways and promotes binge eating.” The Journal of Neuroscience 30.48 (2010): 16399-16407.