Adiposity profile in the dwarf rat: an unusually lean model of profound growth hormone deficiency.
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.
Davies
Jeffrey S
JS
School of Biosciences, Cardiff University, Cardiff, UK.
Gevers
Evelien F
EF
Stevenson
Amy E
AE
Coschigano
Karen T
KT
El-Kasti
Muna M
MM
Bull
Melanie J
MJ
Elford
Carole
C
Evans
Bronwen A J
BA
Kopchick
John J
JJ
Wells
Timothy
T
D050153:Abdominal Fat / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight / Q000502:physiology; D015331:Cohort Studies; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D004435:Eating; D005260:Female; D005503:Food Additives / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D012970:Sodium Glutamate / Q000494:pharmacology; D013977:Tibia / Q000502:physiology
D005503:Food Additives; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D012970:Sodium Glutamate