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

Abstract

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.

• Authors: Jeffrey S Davies, Evelien F Gevers, Amy E Stevenson, Karen T Coschigano, Muna M El-Kasti, Melanie J Bull, Carole Elford, Bronwen A J Evans, John J Kopchick, Timothy Wells
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 292 Issue 5 Pg. E1483-94 (May 2007) ISSN: 0193-1849 [Print] United States
• PMID: 17264226 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Food Additives
• Leptin
• Insulin-Like Growth Factor I
• Sodium Glutamate

Topics

• Abdominal Fat (metabolism)
• Animals
• Animals, Genetically Modified
• Body Weight (physiology)
• Cohort Studies
• Dwarfism, Pituitary (metabolism)
• Eating
• Female
• Food Additives (pharmacology)
• Insulin-Like Growth Factor I (metabolism)
• Leptin (blood, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Rats
• Sodium Glutamate (pharmacology)
• Tibia (physiology)