C57BL/6J mice as a polygenic developmental model of diet‐induced obesity. Issue 7 (11th April 2017)

• Record Type: Journal Article
• Authors: Chu, Dinh‐Toi; Malinowska, Elzbieta; Jura, Magdalena; Kozak, Leslie P.
• Is Part Of: Physiological reports. Volume 5:Issue 7(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-04-11
• Subjects: Developmental control of obesity -- diet‐induced obesity -- epigenetic mechanisms of obesity -- genetic variation of obesity -- lipogenic genes; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13093
• Languages: English
• ISSNs: 2051-817X

Abstract

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 the Sfrp5 promoter and binding of acetylated histones to Sfrp5 and Acly promoter 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. Abstract : Genetic variation of diet‐induced obesity between C57BL/6J (B6) and 129S mice depends on developmental age. Under an obesogenic diet, B6 mice did not develop obesity until they were 8 weeks‐of‐age. The genes and molecular networks of lipogenesis contribute to excessive lipid accumulation in fat depots of B6 mice at age weeks of age. Changes in the expression of these genes and their chromatin structures also followed development, but the latter were not tightly associated with variation in obesity between mouse strains.