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Adiposity profile in the dwarf (dw/dw) rat: an unusually lean model of profound growth hormone deficiency

Davies, Jeffrey Stephens, Gevers, Evelien F., Stevenson, Amy Elizabeth, Coschigano, Karen T., El-Kasti, Muna Mustafa, Bull, Melanie J., Elford, Carole., Evans, Bronwen Alice James ORCID:, Kopchick, John J. and Wells, Timothy ORCID: 2007. Adiposity profile in the dwarf (dw/dw) rat: an unusually lean model of profound growth hormone deficiency. American Journal of Physiology - Endocrinology and Metabolism 292 (5) , E1483-E1494. 10.1152/ajpendo.00417.2006

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This study describes the previously uncharacterized ontogeny and regulation of truncal adipose reserves in the profoundly GH-deficient dwarf (dw/dw) rat. We show that, despite normal proportionate food intake, dw/dw rats develop abdominal leanness and hypoleptinemia (circulating leptin halved in dw/dw males, P < 0.05) during puberty. This contrasts with the hyperleptinemia seen in moderately GH-deficient Tgr rats (circulating leptin doubled at 6 wk of age, P < 0.05) and in GH receptor-binding protein (GHR/BP)-null mice (circulating leptin doubled; P < 0.05). This lean/hypoleptinemic phenotype was not completely normalized by GH treatment, but dw/dw rats developed abdominal obesity in response to neonatal MSG treatment or maintenance on a high-fat diet. Unlike Tgr rats, dw/dw rats did not become obese with age; plasma leptin levels and fat pad weights became similar to those in wild-type rats. In contrast with truncal leanness, tibial marrow adiposity was normal in male and doubled in female dwarves (P < 0.01), this increase being attributable to increased adipocyte number (P < 0.01). Neonatal MSG treatment and high-fat feeding elevated marrow adiposity in dw/dw rats by inducing adipocyte enlargement (P < 0.05). These results demonstrate that, despite lipolytic influence of GH, severe GH deficiency in dw/dw rats is accompanied by a paradoxical leanness. This lean/hypoleptinemic phenotype is not solely attributable to reduced GH signaling and does not appear to result from a reduction in nutrient intake or the ability of dw/dw adipocytes to accumulate lipid. Disruption of preadipocyte differentiation or adipocyte proliferation in the dw/dw rat may lead to the development of this unusually lean/hypoleptinemic phenotype.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Adipose tissue; Bone marrow fat; Leptin; Dwarfism
ISSN: 1522-1555
Last Modified: 17 Oct 2022 08:32

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