Gene Monitoring in Obesity-Induced Metabolic Dysfunction in Rats: Preclinical Data on Breast Neoplasia Initiation

Area of Science:

• Oncology
• Metabolic Science
• Animal Models

Background:

• Obesity and metabolic dysfunction are key risk factors for luminal breast cancer.
• Existing preclinical models fail to fully capture the metabolic and immune interactions in breast cancer development.

Purpose of the Study:

• To develop and characterize an immunocompetent rat model of luminal breast cancer using a cafeteria diet.
• To investigate the metabolic, histological, and molecular changes associated with diet-induced obesity in breast cancer development.

Main Methods:

• Female rats were fed a cafeteria diet or standard chow from weaning.
• Longitudinal evaluation of metabolic parameters, plasma biomarkers, mammary gland histology, tumor incidence, and gene expression.
• Dietary reversal subgroup analyzed to assess molecular alteration reversibility.

Main Results:

• Cafeteria diet induced significant obesity and elevated leptin levels.
• Histology revealed increased benign lesions and earlier development of fibroadenoma and luminal carcinoma.
• Tumors showed luminal phenotype, low Ki67, and elevated PAI-1; gene expression changes included early ID1/COX2 downregulation and later MMP2/THBS1/TWIST1/PAI-1 upregulation.

Conclusions:

• The cafeteria diet rat model effectively recapitulates key features of obesity-associated luminal breast cancer.
• This model provides a valuable platform for studying early tumorigenic mechanisms and prevention strategies in an immunocompetent setting.
• Early molecular alterations are identifiable, suggesting potential intervention points for obesity-driven breast cancer.