Differential susceptibility to obesity between male, female and ovariectomized female mice

Abstract

Background: The prevalence of obesity has increased dramatically. A direct comparison in the predisposition to obesity between males, premenopausal females, and postmenopausal females with various caloric intakes has not been made. To determine the effects of sex and ovarian hormones on the susceptibility to obesity, we conducted laboratory studies with mice. To eliminate confounders that can alter body weight gain, such as age and food consumption; we used mice with the same age and controlled the amount of calories they consumed.

Methods: We determined sex-specific susceptibility to obesity between male, non-ovariectomized female, and ovariectomized female mice. To compare susceptibility to gaining body weight between males and females, animals from each sex were exposed to either a 30% calorie-restricted, low-fat (5% fat), or high-fat (35% fat) diet regimen. To establish the role of ovarian hormones in weight gain, the ovaries were surgically removed from additional female mice, and then were exposed to the diets described above. Percent body fat and percent lean mass in the mice were determined by dual energy x-ray absorptiometry (DEXA).

Results: In all three diet categories, male mice had a greater propensity of gaining body weight than female mice. However, ovariectomy eliminated the protection of female mice to gaining weight; in fact, ovariectomized female mice mimicked male mice in their susceptibility to weight gain. In summary, results show that male mice are more likely to become obese than female mice and that the protection against obesity in female mice is eliminated by ovariectomy.

Conclusion: Understanding metabolic differences between males and females may allow the discovery of better preventive and treatment strategies for diseases associated with body weight such as cancer and cardiovascular disease.

Figure 1

A, shows the body weight profiles for male, female and OVX female C57BL/6 mice fed CR, LF, or HF diets for 20 weeks. Male mice had a greater propensity to gain weight and become obese than female mice (p < 0.05). However, ovariectomy removed the female mice's protection against gaining weight, and in fact, ovariectomized female mice patterned like male mice in their susceptibility to weight gain (p > 0.05). Within male and female mice, after week 10 the body weights were significantly different among all groups (CR vs. LF vs. HF), before then only the CR mice had significantly lower body weights than LF and HF mice at week 5 (p < 0.05). For female vs. male mice (CR male vs. CR female, LF male vs. LF female, HF male vs. HF female) values were significant different at all time points respectively (p < 0.005). However, values were not significantly different between male and OVX female mice (p > 0.005). Percent body fat was determined by DEXA. Abbreviations: 30% calorie-restricted diet (CR), 5% low-fat diet (LF), 35% high-fat diet (HF). B, shows the percent body fat levels in male, female, and OVX-female C57BL/6 mice. Body fat levels between male and female mice were significantly different, with male mice having more body fat in all three diet categories than female mice (p < 0.05). Body fat levels in ovariectomized female mice were almost identical to those of male mice (within each category, male CR vs. CR OVX-female).