Exposure to early-life stress impairs weight-loss maintenance success in mice

ObjectiveThe impact of early-life stress on weight-loss maintenance is unknown.MethodsMice underwent neonatal maternal separation (NMS) from 0 to 3 weeks and were weaned onto a high-fat sucrose diet (HFSD) from 3 to 20 weeks. Calorie-restricted weight loss on a low-fat sucrose diet (LFSD) occurred over 2 weeks to induce a 20% loss in body weight, which was maintained for 6 weeks. After weight loss, half of the mice received running wheels, and the other half remained sedentary. Mice were then fed ad libitum on an HFSD or LFSD for 10 weeks and were allowed to regain body weight.ResultsNMS mice had greater weight regain, total body weight, and adiposity compared with naive mice. During the first week of refeeding, NMS mice had increased food intake and were in a greater positive energy balance than naive mice. Female mice were more susceptible to NMS-induced effects, including increases in adiposity. NMS and naive females were more susceptible to HFSD-induced weight regain. Exercise was beneficial in the first week of regain in male mice, but, long-term, only those on the LFSD benefited from exercise. As expected, HFSD led to greater weight regain than LFSD.ConclusionsEarly-life stress increases weight regain in mice.