Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity

Lipids in Health and Disease, Sep 2010

Background The Berlin Fat Mouse Inbred (BFMI) line is a new mouse model for obesity, which was long-term selected for high fatness. Peroxisome proliferator-activated receptors (PPARs) are involved in the control of energy homeostasis, nutrient metabolism and cell proliferation. Here, we studied the expression patterns of the different Ppar genes and the genes in the PPAR pathway in the BFMI line in comparison to physiological changes. Results At the age of 10 weeks, the BFMI mice exhibited marked obesity with enlarged adipocytes and high serum triglycerides concentrations in comparison to the often used mouse line C57BL/6 (B6). Between these two lines, gene expression analyses revealed differentially expressed genes belonging to the PPAR pathway, in particular genes of the lipogenesis and the fatty acid transport. Conclusion Surprisingly, the Ppar-α gene expression was up-regulated in liver and Ppar-γ gene expression was down-regulated in the white adipose tissue, indicating the activation of a mechanism that counteracts the rise of obesity.

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Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity

Lipids in Health and Disease Genetic and diet effects on Ppar-a and Ppar-g signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity Asja Wagener 0 3 Helge F Goessling 0 3 Armin O Schmitt 0 3 Susanne Mauel 2 Achim D Gruber 2 Richard Reinhardt 1 Gudrun A Brockmann 0 3 0 Humboldt-Universitat zu Berlin, Department for Crop and Animal Sciences , Invalidenstrae 42, 10115 Berlin , Germany 1 Max-Planck-Institut fur molekulare Genetik , Ihnestrae 73, 14195 Berlin , Germany 2 Freie Universitat Berlin, FB Veterinarmedizin, Institut fur Tierpathologie , Robert-von-Ostertag-Strae 15, 14163 Berlin , Germany 3 Humboldt-Universitat zu Berlin, Department for Crop and Animal Sciences , Invalidenstrae 42, 10115 Berlin , Germany Background: The Berlin Fat Mouse Inbred (BFMI) line is a new mouse model for obesity, which was long-term selected for high fatness. Peroxisome proliferator-activated receptors (PPARs) are involved in the control of energy homeostasis, nutrient metabolism and cell proliferation. Here, we studied the expression patterns of the different Ppar genes and the genes in the PPAR pathway in the BFMI line in comparison to physiological changes. Results: At the age of 10 weeks, the BFMI mice exhibited marked obesity with enlarged adipocytes and high serum triglycerides concentrations in comparison to the often used mouse line C57BL/6 (B6). Between these two lines, gene expression analyses revealed differentially expressed genes belonging to the PPAR pathway, in particular genes of the lipogenesis and the fatty acid transport. Conclusion: Surprisingly, the Ppar-a gene expression was up-regulated in liver and Ppar-g gene expression was down-regulated in the white adipose tissue, indicating the activation of a mechanism that counteracts the rise of obesity. - Background The peroxisome proliferator-activated receptors (PPARs) constitute a family of three genes, which are involved in the control of energy homeostasis and cell proliferation. The PPAR family members have distinct patterns of tissue distribution and tissue specific functions. PPAR-a is predominantly present in liver where it has a critical role in the regulation of nutrient metabolism as it stimulates the uptake and oxidation of fatty acids. PPAR-g is mainly expressed in adipose tissue. It is induced during adipocyte differentiation and is a regulator in the formation of fat cells and lipid accumulation. PPAR- is abundantly expressed throughout the body and it has been proposed to be involved in adipogenesis and energy metabolism [for review, see [1-3]]. Activation of PPAR-a by agonists leads to reduced adiposity and lowered triglyceride levels by reduced food intake [4-6], whereas activation of PPAR-g by agonist stimulates lipid storage and is associated with body weight gain [7,8]. Recently, we have generated the high-fatness selected Berlin Fat Mouse inbred line BFMI as a model for juvenile obesity [9]. BFMI mice harbour natural mutations leading to a five fold increased fat percentage due to hyperphagia at young age and an altered lipid metabolism in comparison to C57BL/6 mice [10,11]. A specific regulation of PPAR genes in the development of obesity in the BFMI mice is very likely. Therefore, the intention of this study was to investigate whether the Ppars and their responsive genes are involved in the fat accumulation of the BFMI line. Our aims were (i) to identify differences in gene regulation of Ppars and their responsive genes between the obese BFMI mouse model and B6 mice as a control and (ii) to analyze responses of PPAR pathway genes to high-fat diet feeding in BFMI mice. Therefore, we analysed transcript amounts of genes belonging to the PPAR pathway in white adipose tissue and liver. Furthermore, we analysed body composition, adipocyte size and serum parameters. Results Phenotypic differences between lines BFMI and B6 To compare the body composition of the two lines, male mice of BFMI and B6 were fed a standard maintenance diet (SMD) until week 10. On SMD, animals of the BFMI line were significantly heavier and had more body fat and lean mass than B6 mice over the entire period (Figure 1). At 10 weeks, mice of the BFMI line were 1.8 times as heavy as B6 mice (41.4 2.9 g and 23.5 1.5 g, respectively). The body weight gain was due to increased fat mass. BFMI mice had almost 10 times as much body fat mass but only 1.5 times as much lean mass as B6 animals. In BFMI mice, fat was accumulated in all three investigated adipose tissues mainly due to enlarged adipocytes (Table 1, Figure 2 and 3). The weight of the liver was slightly higher in10 weeks old BFMI mice compared to B6 mice which could be due to increased fat accumulation in liver of BFMI mice (Table 1, Figure 3). Serum triglyceride concentrations, but not total cholesterol concentrations, were elevated in BFMI mice compared to B6. Feeding of HFD in mice of the BFMI line caused an additional body weight and body fat mass gain (9.0 g and 6 (...truncated)


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Asja Wagener, Helge F Goessling, Armin O Schmitt, Susanne Mauel, Achim D Gruber, Richard Reinhardt, Gudrun A Brockmann. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity, Lipids in Health and Disease, 2010, pp. 99, 9, DOI: 10.1186/1476-511X-9-99