title: Key regulators of mitochondrial biogenesis are increased in kidneys of growth hormone receptor knockout (GHRKO) mice.
abstract: The growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and highly insulin sensitive. Alterations in mitochondrial biogenesis are associated with aging and various metabolic derangements. We have previously demonstrated increased gene expression of key regulators of mitochondriogenesis in kidneys, hearts and skeletal muscles of GHRKO mice. The aim of the present study was to quantify the protein levels of the following regulators of mitochondriogenesis: peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), AMP-activated protein kinase α (AMPKα), phospho-AMPKα (p-AMPKα), sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), nuclear respiratory factor-1 (NRF-1) and mitofusin-2 (MFN-2) in skeletal muscles and kidneys of GHRKOs in comparison to normal mice. We also were interested in the effects of calorie restriction (CR) and visceral fat removal (VFR) on these parameters. Both CR and VFR improve insulin sensitivity and can extend life span.
  
  
  RESULTS
  The renal levels of PGC-1α, AMPKα, p-AMPKα, SIRT-3, eNOS, p-eNOS and MFN-2 were increased in GHRKOs. In the GHRKO skeletal muscles, only MFN-2 was increased. Levels of the examined proteins were not affected by CR (except for PGC-1α and p-eNOS in skeletal muscles) or VFR.
  
  
  CONCLUSIONS
  GHRKO mice have increased renal protein levels of key regulators of mitochondriogenesis, and this may contribute to increased longevity of these knockouts.
authors.affiliation: Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, IL, USA. adges7@wp.pl
authors.forename: Adam
authors.initials: A
authors.lastname: Gesing
authors.forename: Andrzej
authors.initials: A
authors.lastname: Bartke
authors.forename: Feiya
authors.initials: F
authors.lastname: Wang
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Karbownik-Lewinska
authors.forename: Michal M
authors.initials: MM
authors.lastname: Masternak
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000601:surgery; D007668:Kidney / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010766:Phosphorylation; D011986:Receptors, Somatotropin / Q000235:genetics* / Q000378:metabolism; D056566:Sirtuin 3 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011986:Receptors, Somatotropin; D015534:Trans-Activators; D014157:Transcription Factors; D052250:Nitric Oxide Synthase Type III; C548179:Prkaa1 protein, mouse; D055372:AMP-Activated Protein Kinases; D056566:Sirtuin 3; D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse