The Genetic Elements of the Obesity Paradox in Atherosclerosis Identified in an Intercross Between Hyperlipidemic Mouse Strains

Figure 1. Atherosclerotic lesions (A) and body weight (B) of male and female F2 mice after being fed 12 weeks of a Western diet. Each symbol represents an individual mouse. The short horizontal lines denote the mean values of each group. The p-values derived from the Student’s t-test are shown.

Figure 2. Associations of body weight with atherosclerotic lesion sizes in male and female F2 mice. The regression line was determined using the linear regression model for each sex separately. Each circle represents the values of an individual F2 mouse.

Figure 3. Correlations between body weight and fat mass in two female backcross mouse populations, NZO × 129 mice (A–D) and NZO × C3H (E–H), at 3, 6, 10, and 15 weeks of age. Mice were fed a high-fat diet after being weaned at 3 weeks of age. The regression line and p and r values were determined by linear regression analysis. Each dot represents an individual mouse.

Figure 4. Genome-wide QTL scans for atherosclerotic lesions. (A) All F2 mice were included in QTL analysis using sex as a covariate; (B) all F2 mice were included in QTL analysis using sex as an interactive covariate; (C) only male F2 mice were included in QTL analysis; and (D) only female F2 mice were included in QTL analysis. The X-axis denotes chromosomes 1 through X, and the Y-axis represents the LOD score. The horizontal green and black lines indicate the genome-wide thresholds for suggestive (p < 0.63) and significant linkage (p < 0.05), respectively. Each vertical short black line sitting on the X-axis represents a genetic marker.

Figure 5. Genome-wide QTL scans for body weight. (A) All F2 mice were included using sex as a covariate; (B) all F2 mice were included using sex as an interactive covariate; (C) only male F2 mice were included; and (D) only female F2 mice were included. The X-axis indicates chromosomes 1 through X, and the Y-axis represents the LOD score.

Figure 6. QTL analysis to evaluate the dependence of atherosclerosis QTLs on body weight. (A) Genome-wide scan for atherosclerosis without adjusting for body weight. (B) Genome-wide scan for atherosclerosis after adjustment for body weight. Note the downgradation of chromosome 15 QTL for atherosclerosis from significant to suggestive linkage (pointed by red arrow).