Two-year body composition analyses of long-lived GHR null mice

Abstract

Growth hormone receptor gene-disrupted (GHR-/-) mice exhibit increased life span and adipose tissue mass. Although this obese phenotype has been reported extensively for young adult male GHR-/- mice, data for females and for other ages in either gender are lacking. Thus, the purpose of this study was to evaluate body composition longitudinally in both male and female GHR-/- mice. Results show that GHR-/- mice have a greater percent fat mass with no significant difference in absolute fat mass throughout life. Lean mass shows an opposite trend with percent lean mass not significantly different between genotypes but absolute mass reduced in GHR-/- mice. Differences in body composition are more pronounced in male than in female mice, and both genders of GHR-/- mice show specific enlargement of the subcutaneous adipose depot. Along with previously published data, these results suggest a consistent and intriguing protective effect of excess fat mass in the subcutaneous region.

Figure 1.

Body weight over time for male and female growth hormone receptor gene–disrupted (GHR−/−) mice and littermate controls. Weight measurements were taken every other week from 6 weeks of age until 16 weeks and taken monthly from 16 weeks until 104 weeks or 2 years of age. Data are expressed as mean ± SEM. Two-way repeated measures analysis of variance revealed a significant impact of genotype, F(1,24) = 163.2, p = 2 × 10⁻¹², and gender, F(1,24) = 14.2, p = .001. WT, wild type.

Figure 2.

Absolute fat mass (A and B) and percent fat mass (C and D) for male (A and C) and female (B and D) growth hormone receptor gene–disrupted (GHR−/−) and littermate control (wild-type [WT]) mice. Data are expressed as mean ± SEM.

Figure 3.

Absolute lean mass (A and B) and percent lean mass (C and D) for male (A and C) and female (B and D) growth hormone receptor gene–disrupted (GHR−/−) and littermate control (wild-type [WT]) mice. Data are expressed as mean ± SEM.

Figure 4.

Femoral length (B) and bone mineral density estimates (C) of mid-diaphyseal cortex in male and female growth hormone receptor gene–disrupted (GHR−/−) and wild-type (WT) mice. Bone mineral density estimates were calculated subsequent to scanning on a GE eXplore Locus Small Animal MicroCT Scanner. Data are expressed as mean ± SEM, n = 10 (male GHR−/− and WT), n = 6 (female WT), n = 9 (GHR−/− female). Right femora (A–D) of 2-year-old mice were extracted, mounted in foam, and scanned using the following protocol: 20-μm voxel, 80 kV, 450 μA, and 2000-milliseconds exposure time.

Figure 5.

Absolute and normalized organ weights of male and female growth hormone receptor gene–disrupted (GHR−/−) and wild-type (WT) mice at 2 years of age. Weights of inguinal (SubQ), perigonadal (PG) for the epididymal fat pad in males and the parametrial fat pad in females, retroperitoneal (Retro), mesenteric (Mes), spleen, liver, kidney, and heart were in 105-week-old mice at the time of dissection. Data are expressed as mean ± SEM. Asterisk indicates GHR−/− samples were significantly different than corresponding WT mice.