title: C57BL/6J mice as a polygenic developmental model of diet-induced obesity.
abstract: Susceptibility to obesity changes during the course of life. We utilized the C57BL/6J (B6) and 129S mouse as a genetic model for variation in diet-induced obesity to define the adiposity phenotypes from birth to maturity at 8 weeks-of-age. From birth to 8 weeks-of-age, both male and female 129S mice had significantly higher fat mass and adiposity index than B6 mice, although they were not obese. After 8 weeks-of-age, B6 had greater adiposity/obesity than 129S mice in response to a high fat (HF). We sought to determine the mechanism activating the fat accumulation in B6 mice at 8-weeks-of-age. We used microarray analysis of gene expression during development of inguinal fat to show that molecular networks of lipogenesis were maximally expressed at 8 weeks-of-age. In addition, the DNA methylation analysis of theSfrp5promoter and binding of acetylated histones toSfrp5andAclypromoter regions showed that major differences in the expression of genes of lipogenesis and chromatin structure occur during development. Differences in lipogenesis networks could account for the strain-dependent differences in adiposity up to 8 weeks-of-age; however, changes in the expression of genes in these networks were not associated with the susceptibility to DIO in B6 male mice beyond 8 weeks-of-age.
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Dinh-Toi
authors.initials: DT
authors.lastname: Chu
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Malinowska
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jura
authors.affiliation: Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland l.kozak@pan.olsztyn.pl.
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D019175:DNA Methylation; D004032:Diet / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004041:Dietary Fats; D036341:Intercellular Signaling Peptides and Proteins; C487972:Sfrp5 protein, mouse; D000094742:Secreted Frizzled-Related Proteins
keywords: Developmental control of obesity; diet‐induced obesity; epigenetic mechanisms of obesity; genetic variation of obesity; lipogenic genes