D. Timtchenko et al., Fat storage capacity in growth-selected and control mouse lines is associated with line-specific gene expression and plasma hormone levels, INT J OBES, 23(6), 1999, pp. 586-594
OBJECTIVE: For a detailed understanding of the complex traits growth and fa
t storage, a dissection into single genetic entities is mandatory. Therefor
e, blood plasma concentrations of hormones and the expression of selected g
enes were measured in extremely differentiated mouse lines. Genes were sele
cted as candidates which might influence the complex traits body weight and
fat accumulation, and which are located in chromosomal regions recently id
entified to affect trait differences between the lines.
SUBJECTS AND MEASUREMENTS: The mouse lines were selected for high body weig
ht (DU6), high carcass protein content (DU6P) and unselected controls (DUKs
). In the selected lines DU6 and DU6P, mean body weights at the age of six
weeks were about twice as high as the DUKs, whereas total fat weight was in
creased 2.2-fold in DU6 mice compared to DU6P and 3.2-fold in comparison to
DUKs. Blood plasma concentrations of insulin-like growth factor 1 (IGF-1),
growth hormone (GH), insulin and leptin, were measured in all lines at thr
ee weeks and at six weeks of age. Expression patterns of the genes encoding
growth hormone (Gh), insulin-like growth factor 1 (Igf1), lipoprotein lipa
se (LpI, glycerolphosphate dehydrogenase 1 (GDC-1), and adipocyte protein 2
(Ap2) were analyzed by Northern blot hybridization.
RESULTS: In line DU6, highly significant increased concentrations of insuli
n and leptin were observed at six weeks of age; at this stage, IGF-1 concen
trations were elevated in the two selected lines compared to controls with
maximal concentrations of IGF-1 and GH in DU6P. The amount of mRNA for GH i
n the pituitary gland, for Igf1 in the liver and for LPL in epididymal fat
tissue was significantly elevated in the two selected lines compared to con
trols at the age of three weeks, but not at six weeks. IGF-1 and GDC-1 mRNA
concentrations were significantly higher in the DU6 mice than in the DU6P
(P < 0.01) and the DUKs (P < 0.001) mice examined at both ages.
CONCLUSIONS: The results prove line-specific concentrations of the analyzed
hormones and the transcription amounts of Gh, Igf1, GDC-1 and LpI. The mea
sured differences are either direct genetic effects or secondary changes, r
esulting from different food consumption.