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

• Published in: American journal of physiology: endocrinology and metabolism Vol. 292; no. 5; pp. E1483 - E1494
• Main Authors: Davies, Jeffrey S, Gevers, Evelien F, Stevenson, Amy E, Coschigano, Karen T, El-Kasti, Muna M, Bull, Melanie J, Elford, Carole, Evans, Bronwen A. J, Kopchick, John J, Wells, Timothy
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.05.2007
• Subjects: Abdominal Fat - metabolism; Animals; Animals, Genetically Modified; Body fat; Body Weight - physiology; Cohort Studies; Dwarfism; Dwarfism, Pituitary - metabolism; Eating; Endocrinology; Female; Food Additives - pharmacology; Growth hormones; Insulin-Like Growth Factor I - metabolism; Leptin - blood; Leptin - metabolism; Male; Medical disorders; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Rats; Rodents; Sodium Glutamate - pharmacology; Tibia - physiology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00417.2006

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 )