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

Early life stress increases obesity risk, but its impact on weight loss maintenance is unknown. Mice underwent neonatal maternal separation (NMS) from 0-3 weeks and were weaned onto high fat sucrose diet (HFSD) from 3-20 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 the mice received running wheels (EX) the other half remained sedentary (SED). Mice were then fed ad libitum on HFSD or LFSD for 10 weeks and allowed to regain body weight. NMS mice had greater weight regain, total body weight and adiposity compared to naïve mice. During the first week of refeeding, NMS mice had increased food intake and were in a greater positive energy balance than naïve mice, but total energy expenditure was not affected by NMS. Female mice were more susceptible to NMS-induced effects, including increases in adiposity. NMS and naïve females were more susceptible to HFSD-induce weight regain. Exercise was beneficial in the first week of regain in male mice, but long-term only those on LFSD benefited from EX. As expected, HFSD led to greater weight regain than LFSD.