Cafeteria Diet-Induced Obesity Alters Uterine Function by Disrupting Insulin and Sex Steroid Actions in Rats.

BACKGROUND

The cafeteria diet (CAFD) model leads to obesity in rats, disrupting glucose metabolism, hormonal balance, and ovarian function, which results in macrosomic offspring. Insulin and ovarian hormones are essential for uterine growth, but there is limited research on how CAFD-induced obesity affects uterine function by modulating hormonal concentrations.

OBJECTIVE

This study aimed to assess how CAFD-induced obesity impacts uterine function in adult female rats by analyzing concentration of ovarian steroids and insulin,along with uterine responses.

METHODS

Postweaning female Sprague-Dawley rats (22 d), were divided into a control group fed pelleted rat chow and an obese group fed energy-dense snacks (CAFD) and pelleted rat chow for 32 wk. Body weight, food intake, energy intake, and estrous cycles were monitored during the experiment. After the experimental period, the uterine tissues were evaluated histologically, and protein expression was analyzed using western blotting and immunofluorescence. Serum hormone concentrations were assessed by ELISA, and uterine oxidative stress markers (superoxide dismutase, catalase, reduced glutathione, lipid peroxidase, and vitamin C) were measured using spectrophotometric methods.

RESULTS

CAFD-fed rats exhibited increased body weight, BMI, and abdominal girth, along with hyperglycemia, extended estrous cycles averaging 8.9 d and 40% reduction in uterine weight (P < 0.0001). The expression of proliferating cell nuclear antigen was elevated (P < 0.0001), with a significant increase in uterine cell proliferation. Obese rats showed lower concentrations of superoxide dismutase, reduced glutathione, and vitamin C, whereas concentrations of lipid peroxidase and catalase were higher in uteri (P < 0.0001). Exposure to CAFD significantly reduced serum concentrations of prolactin, progesterone, and estradiol. Moreover, progesterone receptor and its target molecules (Indian hedgehog homolog, peroxisome proliferator-activated receptor γ, and prolactin receptor) were upregulated, whereas estrogen receptor-α (P < 0.0001) and its responsive molecules (vascular endothelial growth factor and homeobox A11) were downregulated (P < 0.0001).

CONCLUSION

Consumption of CAFD causes obesity, which reduces ovarian steroid and insulin secretion and increases oxidative stress in the rat uterus, altering the expression of key molecules vital for uterine function.