Fat storage capacity in growth-selected and control mouse lines is associated with line-specific gene expression and plasma hormone levels

Abstract

OBJECTIVE: For a detailed understanding of the complex traits growth and fat storage, a dissection into single genetic entities is mandatory. Therefore, blood plasma concentrations of hormones and the expression of selected genes were measured in extremely differentiated mouse lines. Genes were selected as candidates which might in¯uence the complex traits body weight and fat accumulation, and which are located in chromosomal regions recently identi®ed to affect trait differences between the lines. SUBJECTS AND MEASUREMENTS: The mouse lines were selected for high body weight (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 increased 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 three weeks and at six weeks of age. Expression patterns of the genes encoding growth hormone (Gh), insulin-like growth factor 1 (Igf1), lipoprotein lipase (Lpl), glycerolphosphate dehydrogenase 1 (GDC-1), and adipocyte protein 2 (Ap2) were analyzed by Northern blot hybridization. RESULTS: In line DU6, highly signi®cant increased concentrations of insulin and leptin were observed at six weeks of age; at this stage, IGF-1 concentrations 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 in the pituitary gland, for Igf1 in the liver and for LPL in epididymal fat tissue was signi®cantly elevated in the two selected lines compared to controls at the age of three weeks, but not at six weeks. IGF-1 and GDC-1 mRNA concentrations were signi®cantly 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-speci®c concentrations of the analyzed hormones and the transcription amounts of Gh, Igf1, GDC-1 and Lpl. The measured differences are either direct genetic effects or secondary changes, resulting from different food consumption.

Liver protein profiles in insulin receptor-knockout mice reveal novel molecules involved in the diabetes pathophysiology

“…However, to the best of our knowledge, we are the first to show in IR ϩ/Ϫ and IR Ϫ/Ϫ mice a liver structural alteration linked with metabolic disorder by a specific lipid quantification. Impairment in these regulatory mechanisms in the liver could explain at least in part the anomalous hepatic accumulation of lipids, as reported previously (40). The present data are mainly confirmatory of the evidence that insulin resistance is an important and early factor in the pathogenesis of dyslipidemia and steatosis in subjects prone to developing metabolic syndrome and T2D.…”

Long-term voluntary exercise, representing habitual exercise, lowers visceral fat and alters plasma amino acid levels in mice

“…Further experiments are needed to elucidate the lower plasma IGF-1 level in Exmice. IGF-1 is a factor basically linked to muscular growth [34][35][36]. Exercise leads to the increased weight of skeletal muscle, but we found that the plasma IGF-1 level was lower in Ex-mice.…”

Mice long-term selected for high body mass are more susceptible to body fat deposition in response to a high fat diet due to insufficient increase in heat production

“…At this age, body protein content in DU6i was already about twice that of DUKsi (Timtchenko et al 1999) which coheres with the larger body size of these animals. At an age of 98 d, when mice are fully mature, body fat proportion in DU6i males and females was 2.1 and 4.3 times that of the control strain, respectively.…”