title: Daily energy balance in growth hormone receptor/binding protein (GHR -/-) gene-disrupted mice is achieved through an increase in dark-phase energy efficiency.
abstract: The goal of this study was to examine factors that contribute to energy balance in female GHR -/- mice. We measured energy intake, energy expenditure (EE), fuel utilization, body mass (M(b)) changes and physical activity in 17month-old female GHR -/- mice and their age-matched wild type littermates. The GHR -/- mice were smaller, consumed more food per unit M(b), had greater EE per unit M(b) and had an increase in 24-h EE/M(b) that was similar to the increase in their surface-area-to-volume ratio. Locomotor activity (LMA) was reduced in the GHR -/- mice, but the energetic cost associated with their LMA was greater than in wild type controls. Furthermore, M(b) and LMA were independent explanatory covariates of most of the variance in EE, and when adjusted for M(b) and LMA, the GHR -/- mice had higher EE during both the light and dark phases of the daily cycle. Respiratory quotient was lower in GHR -/- mice during the light phase, which indicated a greater utilization of lipid relative to carbohydrate in these mice. Additionally, GHR -/- mice had higher ratios of caloric intake to EE at several intervals during the dark phase, and this effect was greater and more sustained in the final 3h of the dark phase. Therefore, we conclude that GHR -/- mice are able to overcome the substantial energetic challenges of dwarfism through several mechanisms that promote stable M(b). Relative to wild type mice, the GHR -/- mice consumed more calories per unit M(b), which offset the disproportionate increase in their daily energy expenditure. While GHR -/- mice oxidized a greater proportion of lipid during the light phase in order to meet their energy requirements, they achieved greater energy efficiency and storage during the dark phase through a combination of higher energy consumption and lower LMA.
authors.affiliation: Elixir Pharmaceuticals, Inc., 12 Emily St., Cambridge, MA 02139, USA. longoka@mac.com
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Longo
authors.forename: Darlene E
authors.initials: DE
authors.lastname: Berryman
authors.forename: Bruce
authors.initials: B
authors.lastname: Kelder
authors.forename: Soratree
authors.initials: S
authors.lastname: Charoenthongtrakul
authors.forename: Peter S
authors.initials: PS
authors.lastname: Distefano
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Geddes
authors.forename: John J
authors.initials: JJ
authors.lastname: Kopchick
mesh_terms: D000204:Activity Cycles / Q000502:physiology; D000818:Animals; D004392:Dwarfism / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D050356:Lipid Metabolism / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology; D011986:Receptors, Somatotropin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D011986:Receptors, Somatotropin