changes in gene expression foreshadow diet-induced obesity in genetically identical mice基因表达的变化预示着食源性肥胖基因相同的老鼠.pdfVIP

Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice 1 1 1 1 1 1 2 Robert A. Koza , Larissa Nikonova , Jessica Hogan , Jong-Seop Rim , Tamra Mendoza , Christopher Faulk , Jihad Skaf , 1* Leslie P. Kozak 1 Pennington Biomedical Research Center, Baton Rouge, Louisiana, United States of America, 2 Applied Biosystems, Foster City, California, United States of America High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4- fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansio