Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency
1 School of Biosciences, Cardiff University, Cardiff; 2 Division of Molecular Neuroendocrinology, National Institute of Medical Research, London, United Kingdom; 3 Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio; 4 Department of Child Health, Wales C...
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Published in | American journal of physiology: endocrinology and metabolism Vol. 292; no. 5; pp. E1483 - E1494 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Physiological Society
01.05.2007
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Subjects | |
Online Access | Get full text |
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Summary: | 1 School of Biosciences, Cardiff University, Cardiff; 2 Division of Molecular Neuroendocrinology, National Institute of Medical Research, London, United Kingdom; 3 Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio; 4 Department of Child Health, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom; and 5 Edison Biotechnology Institute, Ohio University, Athens, Ohio
Submitted 14 July 2006
; accepted in final form 15 January 2007
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.
adipose tissue; bone marrow fat; leptin; dwarfism
Address for reprint requests and other correspondence: T. Wells, School of Biosciences, Cardiff University, Cardiff, CF10 3US, UK (e-mail: wellst{at}cardiff.ac.uk ) |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0193-1849 1522-1555 |
DOI: | 10.1152/ajpendo.00417.2006 |