Funk 2015 Abstract MiPschool Greenville 2015
|Isolated mitochondria from liver and brain of long-lived growth hormone receptor gene disrupted mice demonstrate reduced respiration rates.|
Event: MiPschool Greenville 2015
Growth hormone (GH) receptor gene disrupted mice (GHR-/-) are dwarf with low levels of IGF-1, high levels of GH, and increased adiposity. Despite obesity, these mice have enhanced insulin sensitivity, are resistant to diabetes, and are long-lived. In contrast, the opposite is observed in bovine (b) GH transgenic mice with excess GH. These mice have high levels of IGF-1 and are giant and lean, with impaired insulin sensitivity and decreased lifespan. Determining the mechanisms involved in this shift in glucose homeostasis may prove crucial for understanding GH’s influence on lifespan in these mice.
In the current study, we isolated mitochondria from livers and brains of GHR-/- mice, as well as from the livers of bGH transgenic mice. Isolated mitochondria were analyzed in vitro using a Seahorse XFe24 Analyzer. In ATP coupled experiments, we determined that mitochondria from GHR-/- livers and brain have reduced State 3 respiration in both the coupled and uncoupled state, as well as reduced State 4 respiration indicating less proton leakage. Conversely, the opposite was observed in the liver of bGH mice. Electron flow experiments showed that respiration rates of electron transport complexes were similarly affected by changes in GH action.
These results suggest that changes in insulin sensitivity may not be solely responsible for their altered metabolic profiles seen in these two mouse strains. GH may directly or indirectly affect several components of the electron transport chain, and thus the oxidative capacity of isolated mitochondria. Further investigation may reveal how the aerobic capacity of the entire organism is altered as a function of GH action, which may ultimately affect health and longevity. This work was supported by the Diabetes Institute at Ohio University, the AMVETS, and the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll.
Labels: MiParea: Respiration Pathology: Diabetes, Obesity
Organism: Mouse Tissue;cell: Nervous system, Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS
1-Edison Biotech Inst, Ohio Univ, Athens, OH; 2-Dept Biol Sc, Ohio Univ, Athens, OH; 3-Mol Cell Biol Program, Ohio Univ, Athens, OH; 4-School Applied Health Sc and Wellness, College Health Sc and Professions, Ohio Univ, Athens, OH; 5-Dept Biomed Sc, Heritage College Osteopathic Med, Ohio Univ, Athens, OH, USA. - firstname.lastname@example.org