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 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.

Pulse Crop Effects on Gut Microbial Populations, Intestinal Function, and Adiposity in a Mouse Model of Diet-Induced Obesity

“…As described above, mice were fed the Ulman diet from receipt to 5 weeks of age in order to promote dysbiosis that is associated with the obesity phenotype which manifests beginning 8 weeks of age [40]. At 5 weeks of age, mice were randomized to treatment groups.…”

Decreased Efficacy of Doxorubicin Corresponds With Modifications in Lipid Metabolism Markers and Fatty Acid Profiles in Breast Tumors From Obese vs. Lean Mice

“…A HFD was used to induce obesity since reported evidence showed that genetic models of obesity (i.e., ob/ob, db/db, and leptin/ leptin receptor-deficient mice) demonstrated resistance in developing mammary cancer (23). C57BL6 mice are particularly sensitive to DIO (24). Forty mice (n = 40) were randomly assigned into two equal groups (n = 20) and allocated one of two respective diets for 12 weeks (Figure 1).…”

Sexually Dimorphic Response of Increasing Dietary Intake of High Amylose Wheat on Metabolic and Reproductive Outcomes in Male and Female Mice

“…Eight-week-old inbred C57BL/6 male and female mice (n = 64) were acquired from the SAHMRI specific pathogen-free and PC2 animal facility breeding colony (Adelaide, SA, Australia) from animals originally obtained from The Jackson Laboratory (Bar Harbor, ME, USA). This strain was chosen because it is one of the most widely used inbred strains of laboratory mouse [19], particularly for metabolic studies [20]. Mice of the same sex were group housed, four to a cage, and maintained within a temperature-controlled environment (22 ± 2 • C) under a 12 h light-dark cycle with ad libitum access to food and autoclaved reverse osmosis water throughout the experiment.…”