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

Abstract

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 levels.

Objective: This study assesses how CAFD-induced obesity impacts uterine function in adult female rats by analysing ovarian steroids, insulin levels, and uterine responses.

Materials & methods: Post-weaning female Sprague-Dawley rats (22 days), were divided into a control group fed standard chow and an obese group fed energy-dense snacks (CAFD) and standard chow for 32 weeks. 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 analysed using Western blotting and immunofluorescence. Serum hormone levels were assessed by ELISA, and uterine oxidative stress markers (SOD, CAT, GSH, LPO, and vitamin C) were measured using spectrophotometric methods.

Results: CAFD-fed rats exhibited increased body weight, BMI, and abdominal girth, along with hyperglycaemia, extended estrous cycles averaging 8.9 days and 40% reduction in uterine weight (p<0.05). The expression of PCNA was elevated (p<0.001), with a significant increase in uterine cell proliferation. Obese rats showed lower levels of SOD, GSH, and vitamin C, while levels of LPO and CAT were higher in uteri (p<0.05). Exposure to CAFD significantly reduced serum levels of prolactin, progesterone, and estradiol. Moreover, progesterone receptor and its target molecules (IHH, PPARγ, PRLR) were upregulated, while estrogen receptor-α (p<0.001) and its responsive molecules (VEGF, HOXA11) were downregulated (p<0.05).

Conclusion: Consumption of CAFD caused obesity, leading to hyposecretion of ovarian steroids, insulin and oxidative stress in the uterus, which affected the uterine milieu by altering the expression of key molecules involved in uterine function.