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    Gene expression profile as a precursor of inflammation in mouse models: BFMI860 and C57BL/6NCrl
    (Istanbul University Press, 2024) Doğan, Ayça; Brockmann, Gudrun A.
    Objective: We aimed to investigate the differences in the immune response to body fat content between the genetically mutant obese BFMI860 (BFMI) mouse strain and the lean C57BL/6Ncrl (B6) mouse strain as a control and the effects of obesity on gene expression on inflammation-related pathways in epididymal adipose tissue. Materials and Methods: Six males from each strain were maintained on a standard maintenance diet (SMD) or a high-fat diet (HFD). At the age of 10 weeks, serum and epididymal adipose tissue samples were collected for cytokine and gene expression analyses. RNA samples from epididymal adipose tissue were hybridized using the microarray technique to study the quantitative transcript amounts of genes. Results: Pathway analysis of gene expression data revealed no considerable development of inflammatory state in BFMI and B6 on SMD. Both strains responded to HFD distinctly; the inflammatory state was more prominent in the obese BFMI group than in the lean B6 group. Several genes, such as Adipoq, NFkbia, Plaur, F2r, C3ar1, and Nfatc4 in pathways involved in the immune system have been found to be differentially regulated in BFMI mice. Under the condition of obesity in BFMI mice, the induction of inflammation-related pathways indicates an increased risk of insulin resistance, atherosclerosis, and cardiovascular disease. Conclusion: This study identified distinct expression patterns of genes involved in inflammatory pathways, particularly those associated with the adipocytokine signaling pathway and complement and coagulation cascades, in the epididymal adipose tissue of BFMI and B6 mice. The BFMI strain is a valuable and promising model for clarifying the mechanisms underlying obesity and the activation of inflammation in adipose tissue.
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    Systems genetics of obesity
    (Humana Press Inc., 2017) Brockmann, Gudrun A.; Arends, Danny; Heise, Sebastian; Doğan, Ayça
    Obesity is a complex trait, determined by many genes and influenced by environmental factors. Mapping genomic loci contributing to obesity helps to identify gene variants responsible for differences in the phenotype. However, measuring fat content alone is often not sufficient to identify the underlying gene or genes. Besides in-depth phenotyping, well-designed genetic populations and the combined analysis of data of different origins are necessary to detect one of several genetic determinants. Structured mouse populations and linking information from different experiments help to simplify the complexity in the search for direct genetic effects or factors that are hidden in the genome. In this chapter we present an example of how the physicochemical characterization of adipose tissue in BXD recombinant inbred lines contributes to enlighten the obese phenotype of mice. We describe the search for gene(s) contributing to collagen content in adipose tissue of BXD strains using the GeneNetwork platform. © Springer Science+Business Media New York 2017.