Obesity contributes to many chronic conditions that decrease life quality and longevity, and its global prevalence is increasing. Caloric restriction can lower body weight rapidly in the short term, but weight tends to subsequently rebound as a result of compensatory metabolic changes, such as increased appetite.
Researchers explored a strategy for preventing postdieting weight gain in mice by targeting the appetite-stimulating hormone ghrelin. Mice were fed a high-fat diet from 8–20 weeks of age before being switched to a diet with 40% lower calorie content than their previous diet, leading to substantial weight loss.
Upon beginning the calorie-restricted (CR) diet, mice were injected with an adeno-associated virus expressing either the enzyme butyrylcholinesterase (BChE), which inactivates ghrelin, or a control enzyme, luciferase.After 3 weeks on the CR diet, mice were switched to an unrestricted low-fat diet.
Following the end of the CR diet, mice treated with the BChE virus expressed lifelong high plasma levels of BChE and lower levels of acyl-ghrelin, the active form of ghrelin, than the control-treated mice. BChE-treated mice also consumed fewer calories, regained less weight, and had better glucose tolerance than control-treated mice.
According to the authors, the results suggest the potential of BChE gene therapy for obesity treatment.