title: Lopinavir/Ritonavir Impairs Physical Strength in Association with Reduced Igf1 Expression in Skeletal Muscle of Older Mice.
abstract: BACKGROUND
  Late-middle age HIV patients are prone to fatigue despite effective viral control by antiretroviral therapies. Rodent models to recapitulate this phenotype are still not available.
  
  
  OBJECTIVE
  Drug treatment may compromise muscle strength and physical performance more in older individuals with pre-existing metabolic disorders than normal young ones.
  
  
  METHODS
  Kaletra was given to overweight male mice at late-middle age and normal young adults; both on a rodent diet containing 30% fat calorie. Body composition and grip strength were measured at baseline and after drug treatment. Rota-rod running, insulin and glucose tolerance were measured at the end of the experiment. Drug effect on metabolic activity and spontaneous movements were assessed using the metabolic cage system. Representative muscle and fat tissue were analyzed for protein and mRNA expression. Selected findings were tested using murine C2C12 myotubes.
  
  
  RESULTS
  Kaletra reduced grip strength in both young and older mice but impaired rotarod performance only in the old. Spontaneous movements were also reduced in Kaletra-treated old mice. Kaletra reduced IGF-1 expression in all muscle groups tested for the old and in cultured myotubes but to a less extent in the muscle of young animals. Reduced IGF-1 expression correlated with increased expression of muscle-specific atrogene MAFbx and MuRF1. Kaletra also increased abdominal fat mass markedly in the old animals and to a less extend in the young.
  
  
  CONCLUSIONS
  Long-term Kaletra intake aggravated abdominal obesity and impaired muscle strength. This effect was worse in older animals than in normal young adults.
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Siu
authors.initials: S
authors.lastname: Wong
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Serra
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Deng
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function promoting Anabolic Therapies, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
keywords: Adipose tissue; Age and overweight; HIV protease inhibitor; Insulin resistance; Insulin-like growth factor 1; Muscle; Physical strength and mobility