Male Bovine GH Transgenic Mice Have Decreased Adiposity With an Adipose Depot-Specific Increase in Immune Cell Populations

Benencia, Fabián; Harshman, Stephanie; Duran‐Ortiz, Silvana; Lubbers, Ellen R.; List, Edward O.; Householder, Lara A.; Alnaeeli, Mawadda; Liang, Xiaoyu; Welch, Lonnie R.; Kopchick, John J.; Berryman, Darlene E.

doi:10.1210/en.2014-1794

Cited by 35 publications

(45 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In humans, acromegaly leads to an increase in body water and lean body mass (Ikkos et al 1954, O'Sullivan et al 1994, Kamenický et al 2014, associated with a reduction in body fat (Freda et al 2008, Katznelson 2009. Similarly, giant bovine-GH transgenic mice (bGH) exhibit a lower body fat percentage, smaller WAT deposits and lower serum leptin levels (Berryman et al 2004, Benencia et al 2014. We found that Aip +/− mice exhibit a slightly enhanced total body weight at 3 and 7 months but not at 12 months of age.…”

Section: Discussionmentioning

confidence: 80%

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Lecoq

Zizzari

Hage

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene predispose humans to pituitary adenomas, particularly of the somatotroph lineage. Mice with global heterozygous inactivation of Aip (Aip +/− ) also develop pituitary adenomas but differ from AIP-mutated patients by the high penetrance of pituitary disease. The endocrine phenotype of these mice is unknown. The aim of this study was to determine the endocrine phenotype of Aip +/− mice by assessing the somatic growth, ultradian pattern of GH secretion and IGF1 concentrations of longitudinally followed male mice at 3 and 12 months of age. As the early stages of pituitary tumorigenesis are controversial, we also studied the pituitary histology and somatotroph cell proliferation in these mice. Aip +/− mice did not develop gigantism but exhibited a leaner phenotype than wild-type mice. Analysis of GH pulsatility by deconvolution in 12-month-old Aip +/− mice showed a mild increase in total GH secretion, a conserved GH pulsatility pattern, but a normal IGF1 concentration. No pituitary adenomas were detected up to 12 months of age. An increased ex vivo response to GHRH of pituitary explants from 3-month-old Aip +/− mice, together with areas of enlarged acini identified on reticulin staining in the pituitary of some Aip +/− mice, was suggestive of somatotroph hyperplasia. Global heterozygous Aip deficiency in mice is accompanied by subtle increase in GH secretion, which does not result in gigantism. The absence of pituitary adenomas in 12-month-old Aip +/− mice in our experimental conditions demonstrates the important phenotypic variability of this congenic mouse model.

show abstract

Section: Discussionmentioning

confidence: 80%

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Lecoq

Zizzari

Hage

et al. 2016

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…For example, we have evidence of significant alterations in ECM deposition with bGH mice having marked increases, specifically in the SubQ depot [143]. We also have preliminary data suggesting genotype and depot differences in gene or protein expression related to macrophage and T cell infiltration, angiogenic capacity, beige adipocyte composition, and glucose/lipid metabolism [179]. In fact, most of the unpublished data generated to explore the AT transcriptome in these mice reveal greater differences among depots, especially between SubQ and perigonadal, than among genotypes themselves [179].…”

Section: Obesity and Depot-specific Alterations In Gh Mouse Linesmentioning

confidence: 92%

“…We also have preliminary data suggesting genotype and depot differences in gene or protein expression related to macrophage and T cell infiltration, angiogenic capacity, beige adipocyte composition, and glucose/lipid metabolism [179]. In fact, most of the unpublished data generated to explore the AT transcriptome in these mice reveal greater differences among depots, especially between SubQ and perigonadal, than among genotypes themselves [179]. Clearly, the use of these lines may help unravel the underlying mechanism of how depot differences are established and maintained and provide insight into the novel means to modulate AT mass and obesity.…”

Section: Obesity and Depot-specific Alterations In Gh Mouse Linesmentioning

confidence: 95%

See 1 more Smart Citation

Living Large: What Mouse Models Reveal about Growth Hormone and Obesity

Berryman

Householder

Lesende

et al. 2015

Energy Balance and Cancer

Self Cite

View full text Add to dashboard Cite

Growth hormone (GH) regulates a broad spectrum of biological processes in addition to promoting longitudinal growth. As such, GH influences most organ and cellular systems in the body with adipose tissue being one of its wellestablished targets. This chapter will describe mouse lines with specific alteration in GH action. Mice with increased, decreased, and absence of GH action have a unique phenotype for which clinical equivalents exist (acromegaly, GH deficiency, and Laron syndrome, respectively). Interestingly, these mouse lines demonstrate adiposity profiles that are counterintuitive to health and longevity. That is, mice with excess GH action are lean but insulin resistant, prone to cancer, and short-lived (or "unhealthy lean"). On the other hand, mice with no GH action are obese but insulin sensitive, resistant to cancer, and long-lived (or "healthy obesity"). These extremes in GH action provide fascinating mouse strains with which to study the features of fat that are responsible for metabolic dysfunction and to explore traits that are obligatory for cancer or lifespan.

show abstract

“…As expected, the overexpression of heterologous and homologous GH can lead to giant body with hyperplasia of thymus and spleen, and increased mitogenic response of spleen cells. But the giant mice exhibit a short lifespan and impaired glucose metabolism (Benencia et al 2014).…”

Section: Gh/igf-1 and Insulin/igf-1 Signalingmentioning

confidence: 99%

Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan

2015

View full text Add to dashboard Cite

High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.

show abstract

Male Bovine GH Transgenic Mice Have Decreased Adiposity With an Adipose Depot-Specific Increase in Immune Cell Populations

Cited by 35 publications

References 66 publications

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Mild pituitary phenotype in 3- and 12-month-old Aip-deficient male mice

Living Large: What Mouse Models Reveal about Growth Hormone and Obesity

Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan

Contact Info

Product

Resources

About