Weight restoration on a high carbohydrate refeeding diet promotes rapid weight regain and hepatic lipid accumulation in female anorexic rats

Abstract

BackgroundThere is currently no standard clinical refeeding diet for the treatment of anorexia nervosa (AN). To provide the most efficacious AN clinical care, it is necessary to define the metabolic effects of current refeeding diets.MethodsAn activity-based model of anorexia nervosa (AN) was used in female rats. AN was induced over 7d by timed access to low fat (LF) diet with free access to a running wheel. Plasma hormones/metabolites and body composition were assessed at baseline, AN diagnosis (day 0), and following 28d of refeeding on LF diet. Energy balance and expenditure were measured via continuous indirect calorimetry on days −3 to +3.ResultsAN induction caused stress as indicated by higher levels of corticosterone versus controls (p < 0.0001). The rate of weight gain during refeeding was higher in AN rats than controls (p = 0.0188), despite lower overall energy intake (p < 0.0001). This was possible due to lower total energy expenditure (TEE) at the time of AN diagnosis which remained significantly lower during the entire refeeding period, driven by markedly lower resting energy expenditure (REE). AN rats exhibited lower lipid accumulation in visceral adipose tissues (VAT) but much higher liver accumulation (62 % higher in AN than control; p < 0.05) while maintaining the same total body weight as controls. It is possible that liver lipid accumulation was caused by overfeeding of carbohydrate suggesting that a lower carbohydrate, higher fat diet may be beneficial during AN treatment. To test whether such a diet would be accepted clinically, we conducted a study in adolescent female AN patients which showed equivalent palatability and acceptability for LF and moderate fat diets. In addition, this diet was feasible to provide clinically during inpatient treatment in this population.ConclusionRefeeding a LF diet to restore body weight in female AN rats caused depressed TEE and REE which facilitated rapid regain. However, this weight gain was metabolically unhealthy as it resulted in elevated lipid accumulation in the liver. It is necessary to investigate the use of other diets, such as lower carbohydrate, moderate fat diets, in pre-clinical models to develop the optimal clinical refeeding diets for AN.

Successful management and recovery following severe prolonged starvation in a dog

“…These guidelines were based on extrapolation from common guidelines used in juvenile human anorexia nervosa patients. Rapid refeeding of anorexic rats and human patients in the weeks and months after starvation can result in higher body fat gain relative to lean tissue and increased lipid accumulation in the liver . We hoped to minimize this by limiting the rate of weight gain in this dog.…”

Activity Based Anorexia as an Animal Model for Anorexia Nervosa–A Systematic Review

“…Additionally, the combination of both, food restriction and access to running wheel, elevated total antioxidant plasma levels but also reduced antioxidant parameters in the liver and plasma malondialdehyde levels compared to controls (91), presumably resulting from a reduced need of antioxidant activity in the liver associated with a higher plasma antioxidant capacity. Additionally, during refeeding after development of ABA, female rats displayed a lower resting energy expenditure and total energy expenditure resulting in higher weight gain, although energy intake was lower compared to controls (95). Although controls and ABA rats maintained similar body weights, lipid accumulation in visceral adipose tissue was reduced, while liver fat accumulation was increased in post-ABA rats, probably caused by overfeeding with carbohydrates (95).…”

“…Additionally, during refeeding after development of ABA, female rats displayed a lower resting energy expenditure and total energy expenditure resulting in higher weight gain, although energy intake was lower compared to controls (95). Although controls and ABA rats maintained similar body weights, lipid accumulation in visceral adipose tissue was reduced, while liver fat accumulation was increased in post-ABA rats, probably caused by overfeeding with carbohydrates (95). Therefore, the ABA model can also be used to study the consequences of weight restoration in AN.…”

Implementing High Energy Liquid Nutrition, Omega-3 Fatty Acids and Nutritional Supplements for the Treatment of Anorexia Nervosa

“…Further, our data clearly showed a better weight gain in patients with a carbohydrate rich nutrition. We are aware of the higher risk of a refeeding syndrome in these patients as recently proved by Gilles et al in an animal model 24 . However, we did not observe a refeeding syndrome while using supplements according the NICE guideline.…”