Objective: The goal of this study was to investigate the combined effects of ovariectomy (OVX) and high-fat diet (HF) on insulin sensitivity and pancreatic remodeling in C57BL/6 mice treated with bezafibrate.
Methods: Female C57BL/6 mice were subjected to OVX or surgical procedure without removal of the ovary (SHAM). Animals received standard chow (SC; 10% lipids) or HF (60% lipids). After 13 weeks on the diets, the animals were subdivided into six groups based on diet, bezafibrate treatment, or both: SHAM-SC, SHAM-HF, SHAM-HFBz, OVX-SC, OVX-HF, and OVX-HFBz. After treatment for 5 weeks, the pancreas was removed and analyzed using morphometry, stereological tools, immunostaining, and multiplex assay kits.
Results: SHAM-HF and OVX-HF mice showed increased fasting glucose levels, plasma insulin levels, homeostasis model of assessment for insulin resistance index, body mass, islet hypertrophy, β-cell mass, and insulin immunostaining, but decreased GLUT2 immunostaining. Bezafibrate treatment prevented islet hypertrophy and reduced body mass, plasma insulin levels, and homeostasis model of assessment for insulin resistance index.
Conclusions: OVX combined with HF accentuates the effects of menopause, leading to the development of insulin resistance. Bezafibrate treatment reduces body mass, plasma insulin levels, and pancreatic islet hypertrophy in mice fed HF.