title: Long-term physiological alterations and recovery in a mouse model of separation associated with time-restricted feeding: a tool to study anorexia nervosa related consequences.
abstract: BACKGROUND
  Anorexia 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.
  
  
  OBJECTIVE
  To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.
  
  
  METHODS
  C57Bl/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.
  
  
  RESULTS
  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, 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.
  
  
  CONCLUSIONS
  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. 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.
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Zgheib
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France; UMR INSERM 837, Développement et Plasticité du Cerveau Post-natal, Lille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Méquinion
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lucas
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Leterme
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Olfa
authors.initials: O
authors.lastname: Ghali
authors.affiliation: UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Tolle
authors.affiliation: UMR-S 894 INSERM, Centre de Psychiatrie et Neurosciences, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Zizzari
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; UMR INSERM 837, Développement et Plasticité du Cerveau Post-natal, Lille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bellefontaine
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France; Service de Rhumatologie, Hôpital Roger Salengro, CHU Lille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Legroux-Gérot
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hardouin
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Broux
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; UMR INSERM 837, Développement et Plasticité du Cerveau Post-natal, Lille, France; Université de Lille1, Villeneuve d'Ascq, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Viltart
authors.affiliation: Université Lille Nord de France, Boulogne sur Mer, France; Physiopathologie des Maladies Osseuses Inflammatoires, Boulogne sur Mer, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Chauveau
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D000856:Anorexia Nervosa / Q000097:blood / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D001010:Anxiety, Separation / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D001823:Body Composition; D004195:Disease Models, Animal; D004435:Eating; D030762:Estrous Cycle; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010641:Phenotype; D012098:Reproduction; D013997:Time Factors; D015431:Weight Loss
chemical_list: D052242:Adiponectin; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone
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