Quantitative trait loci for individual adipose depot weights in C57BL/6ByJ x 129P3/J F2 mice

Abstract

To understand how genotype influences fat patterning and obesity, we conducted an autosomal genome scan using male and female F(2) hybrids between the C57BL/6ByJ and 129P3/J parental mouse strains. Mice were studied in middle-adulthood and were fed a low-energy, low-fat diet during their lifetime. We measured the weight of the retroperitoneal adipose depot (near the kidney) and the gonadal adipose depot (near the epididymis in males and ovaries in females). An important feature of the analysis was the comparison of linkage results for absolute adipose depot weight and depot weight adjusted for body size, i.e., relative weight. We detected 67 suggestive linkages for six phenotypes, which fell into one of three categories: those specific to absolute but not relative depot weight (Chr 5, 11, and 14), those specific to relative but not absolute depot weight (Chr 9, 15, and 16), and those involving both (Chr 2 and 7). Some quantitative trait loci (QTLs) affected one adipose depot more than another: Retroperitoneal depot weight was linked to Chr 8, 11, 12, and 17, but the linkage effects for the gonadal depot were stronger for Chr 5, 7, and 9. Several linkages were specific to sex; for instance, the absolute weight of gonadal fat was linked to Chromosome 7 in male (LOD = 3.4) but not female mice (LOD = 0.2). Refining obesity as a phenotype may uncover clues about gene function that will assist in positional cloning efforts.

Fig. 1

Adipose depot weight of F₂, mice expressed as standardized residuals after multiple regression analysis using age and litter size as convariates, is plotted against body length or body weight. Linear regressions between body length or body weight and adipose depot weight are shown as lines, and individual data points are shown as black circles (retroperitoneal) or gray triangles (gonadal). Body weight positively correlates with both the weight of the retroperitoneal adipose depot (r value differs from 0.0; p = 1.9 × 10⁻⁷) and the weight of the gonadal depot (p = 1.3 × 10⁻⁵). Body length is related to the weight of the retroperitoneal depot but these relationships are not statistically significant (RP, p = 0.22; GON, p = 0.12). Correction for both body weight and body length removes all effects of body size on adipose depot weights (all final r values are 0.0).

Fig. 2

Genome scan results for the retroperitoneal adipose depot (red lines), the gonadal adipose depot (blue lines), and the sum of both depots (black lines), expressed as both absolute (solid lines) and relative to body size (dashed lines). The horizontal lines indicate the suggestive thresholds for additive (1.9), dominant and recessive (2.3), and free (2.8) models. Data are plotted for the free model and therefore some linkages do not meet the criterion for suggestive linkage for a free model but do meet the threshold for a constrained model. See Table 5 and text for other details.

Fig. 3

Genome scan results for the retroperitoneal adipose depot (upper panel), gonadal adipose depot (middle panel), and sum of both the retroperitoneal and gonadal adipose depots (lower panel), either absolute (solid lines) or relative to body size (dashed lines), for females (pink lines) and males (blue lines). The horizontal dotted line indicates the threshold for suggestive linkage for different models. See Table 5 and text for other details.