Two-Year Body Composition Analyses of Long-Lived GHR Null Mice

School of Human and Consumer Sciences, College of Health and Human Services, Ohio University, Athens, OH 45701, USA.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences (Impact Factor: 5.42). 11/2009; 65(1):31-40. DOI: 10.1093/gerona/glp175
Source: PubMed

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.

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Available from: Patrick M O'Connor, Sep 09, 2014
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    • "We also found that GHR-/- mice are protected from age-related accumulation of hepatic triglycerides. Others were not able to detect statistically significant increases in hepatic triglycerides in these mice [36], perhaps because of sample size, animal ages, or assay methods. Nevertheless, decreased age-related redistribution of lipid in mice with diminished GH activity supports the assertion that site-specific lipid deposition is linked with healthspan and longevity. "
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    ABSTRACT: The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible.
    Aging 07/2014; 6(7). · 4.70 Impact Factor
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    • "In fact, significantly lower levels of growth hormone receptor (GHR) mRNA have been found in adipose tissues of obese human subjects, as compared with the lean human counterparts [24]. Furthermore, mice with growth hormone receptor deficiency (GHR−/−) have a greater percent fat mass but with no significant differences in absolute fat mass through the life, and animals with lean mass show an opposite trend [25]. It has been found that the organization of fish intestine is similar to that of mammals, and more importantly many homologous genes which are regulated by gut microbes in mammals show similar expression responses in fish [26]. "
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    PLoS ONE 05/2013; 8(5):e64577. DOI:10.1371/journal.pone.0064577 · 3.23 Impact Factor
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    • "However, long-lived Snell dwarf mice are obese and hyperleptinaemic in old age [41], and have unaltered fasting (3–6 h) insulin and glucose levels relative to control mice at 20–23 months of age [41,42]. Percentage fat mass, normalized to total body mass, was also elevated in GHR-KO mice over a 2 year period relative to controls, with the increased adiposity more apparent in males [43]. "
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