title: Perpetuating effects of androgen deficiency on insulin resistance.
abstract: Androgen deprivation therapy (ADT) is commonly used for treatment of prostate cancer but is associated with side effects, such as sarcopenia and insulin resistance. The role of lifestyle factors such as diet and exercise on insulin sensitivity and body composition in testosterone-deficient males is poorly understood. The aim of the present study was to examine the relationships between androgen status, diet and insulin sensitivity.
  
  
  
  Middle-aged (11-12 years old) intact and orchidectomized male rhesus macaques were maintained for 2 months on a standard chow diet and then exposed for 6 months to a Western-style, high-fat/calorie-dense diet (WSD) followed by 4 months of caloric restriction (CR). Body composition, insulin sensitivity, physical activity, serum cytokine levels and adipose biopsies were evaluated before and after each dietary intervention.
  
  
  
  Both intact and orchidectomized animals gained similar proportions of body fat, developed visceral and subcutaneous adipocyte hypertrophy and became insulin resistant in response to the WSD. CR reduced body fat in both groups but reversed insulin resistance only in intact animals. Orchidectomized animals displayed progressive sarcopenia, which persisted after the switch to CR. Androgen deficiency was associated with increased levels of interleukin-6 and macrophage-derived chemokine (C-C motif chemokine ligand 22), both of which were elevated during CR. Physical activity levels showed a negative correlation with body fat and insulin sensitivity.
  
  
  
  Androgen deficiency exacerbated the negative metabolic side effects of the WSD such that CR alone was not sufficient to improve altered insulin sensitivity, suggesting that ADT patients will require additional interventions to reverse insulin resistance and sarcopenia.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Cameron
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jain
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rais
authors.affiliation: Divisions of Obesity and Metabolism, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: White
authors.affiliation: Division of Hematology and Medical Oncology, OHSU Knight Cancer Institute, Portland, OR, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Beer
authors.affiliation: School of Nursing, Oregon Health and Science University, Portland, OR, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kievit
authors.affiliation: School of Nursing, Oregon Health and Science University, Portland, OR, USA.
authors.forename: K
authors.initials: K
authors.lastname: Winters-Stone
authors.affiliation: Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA.
authors.forename: I
authors.initials: I
authors.lastname: Messaoudi
authors.affiliation: Divisions of Obesity and Metabolism, Oregon National Primate Research Center, Beaverton, OR, USA.
authors.forename: O
authors.initials: O
authors.lastname: Varlamov
mesh_terms: D000728:Androgens / Q000172:deficiency* / Q000502:physiology; D000818:Animals; D001823:Body Composition / Q000502:physiology*; D031204:Caloric Restriction; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D007006:Hypogonadism / Q000473:pathology*; D007333:Insulin Resistance / Q000502:physiology*; D015850:Interleukin-6; D008055:Lipids; D008253:Macaca mulatta; D008297:Male; D009765:Obesity / Q000473:pathology*; D010805:Physical Conditioning, Animal; D011944:Receptors, Androgen
chemical_list: D000728:Androgens; D015850:Interleukin-6; D008055:Lipids; D011944:Receptors, Androgen