Abstract
BackgroundAnorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.AimTo explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.MethodsC57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.ResultsMimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.ConclusionThis study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.
Highlights
Chronic food restriction and the pathologic fear of weight gain are major symptoms described in restrictive-type anorexia nervosa (AN) patients
Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, growth hormone (GH)/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were changed
This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations
Summary
Chronic food restriction and the pathologic fear of weight gain are major symptoms described in restrictive-type anorexia nervosa (AN) patients This disease mainly affects young girls with an average prevalence of 0.3% [1] and carries a high rate of morbidity, with osteoporosis being one of its major complications, occurring in 20–30% of cases depending on the studies [2,3], and high fracture risk [4]. Biological analyses of patients do not reveal alterations of calcemia, phosphatemia and vitamin D level [5] This psychiatric disease results in severe weight loss as shown by a mean body weight of 71% of that of healthy well-balanced weight controls, calculated from 10 different studies, and is frequently associated with chronic stress [6,7]. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment
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