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 17 month-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 3 h 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.