Restrictive type anorexia nervosa (AN) patients show numerous alterations that cause long-term physiological damages. We have used a mouse model of chronic food restriction combined with voluntary exercise, that mimics parts of the AN pathology, to determine the metabolic and endocrine alterations and investigate the potential positive effect of physical activity. Two 8-weeks old female mice (FRW) were placed in a cage equipped with a wheel and submitted to a 15-days protocol (short-term) consisting of a progressive food restriction from 30 to 50 % then extended to 55 days (long-term). FRW mice were compared to ad libitum (AL), ad libitum and wheel (ALW) and food restriction (FR) mice. On the short-term, FRW mice showed a stable 20% decrease of the body weight, associated with a decrease in the lean and fat masses, and an increased physical activity during light time. When the protocol was extended on long-term, FRW mice regained weight compared to FR mice with a daily decreased physical activity (night). FR and FRW mice displayed also distinct profiles of respiratory exchange ratio (RER), energy expenditure (EE) and fat oxidation. Like in patients, food restricted groups displayed an increase of RER following carbohydrate intake associated with lower daily EE levels. Endocrine alterations were also observed: FR and FRW mice displayed a similar hormonal profile with hypoleptinemia, hypercorticosteronemia and hyperghrelinemia at short-term whereas protocol expansion induced a normalization and a decrease of leptin and of corticosterone plasma levels respectively, only in FRW mice. In conclusion, the FRW mice compared to FR mice presented alterations that are indicative of a global differential adaptation of the organism to this severe condition of chronic food restriction in which exercise plays a key role.