title: Effect of mTOR inhibitor on body weight: from an experimental rat model to human transplant patients.
abstract: The aim was to study the influence of sirolimus (SRL) on body weight in a rat model and in kidney transplant patients. Wistar rats (15 weeks old) were either treated with vehicle (VEH; n = 8) or SRL (n = 7) 1.0 mg/kg three times per week for 12 weeks. Body mass and food intake were measured weekly. Adipocyte diameter was determined in hematoxylin-eosin stains. The body mass index (BMI) obtained from clinical kidney transplant trials comparing SRL-based with cyclosporine-based therapy was analyzed.
  
  
  METHODS
  SRL produced a decrease of the weight gain curve. At the end of the study, mean body weight in the SRL group was lower than in the VEH group (356 vs. 507 g, P < 0.01) in spite of comparable food intake normalized for body weight was not different. Mean adipocyte diameter was 36 mum in VEH and 25 mum in SRL rats (P = 0.009). Mean SRL blood trough concentration was 38 ng/ml. Kidney transplant patients: Two years after transplantation, BMI was significantly lower in the SRL-based treatment arm compared to cyclosporine (24.17 +/- 2.99 vs. 25.97 +/- 5.01 kg/m(2), P = 0.031). SRL treatment leads to less body mass. Adipocyte cell diameter was reduced in SRL-treated animals. A possible explanation may be the effects of SRL on metabolic regulation and cell growth.
authors.affiliation: Department of Nephrology and Renal Transplantation, Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Hospital Clínic i Provincial de Barcelona, Barcelona, Spain. jrovira1@clinic.ub.es
authors.forename: Jordi
authors.initials: J
authors.lastname: Rovira
authors.forename: Edgar
authors.initials: E
authors.lastname: Marcelo Arellano
authors.forename: James T
authors.initials: JT
authors.lastname: Burke
authors.forename: Yves
authors.initials: Y
authors.lastname: Brault
authors.forename: Daniel
authors.initials: D
authors.lastname: Moya-Rull
authors.forename: Elisenda
authors.initials: E
authors.lastname: Bañón-Maneus
authors.forename: María J
authors.initials: MJ
authors.lastname: Ramírez-Bajo
authors.forename: Alex
authors.initials: A
authors.lastname: Gutiérrez-Dalmau
authors.forename: Ignacio
authors.initials: I
authors.lastname: Revuelta
authors.forename: Luis F
authors.initials: LF
authors.lastname: Quintana
authors.forename: Josep M
authors.initials: JM
authors.lastname: Campistol
authors.forename: Fritz
authors.initials: F
authors.lastname: Diekmann
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects*; D016572:Cyclosporine / Q000627:therapeutic use; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D011494:Protein Kinases / Q000187:drug effects*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011494:Protein Kinases; C546842:MTOR protein, human; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus