Effects of bezafibrate treatment on pancreatic remodeling and insulin resistance in ovariectomized C57BL/6 mice fed high-fat diet

T. Faria; A. Ludgero-Correia; M. Aguilla; C. Mandarim-de-Lacerda

Introduction: Ovariectomized C57BL/6 mice are a good model to study the postmenopausal stage. It has been reported that high-fat diet (HFD) augments the body fat mass and insulin resistance (IR) in animal models. Goal of this study was to investigate the combined effects of ovariectomy (OVX) and HFD on insulin sensitivity and pancreatic remodeling in C57BL/6 mice treated with bezafibrate.

Methods: Female C57BL/6 mice were subjected to surgical OVX and surgery without removal of the ovary (SHAM). Animals received standard chow diet (SC 10% lipids) or high-fat diet (HF 60% lipids). After 13 weeks of diet, the animals were subdivided in six groups (n=5), diet and/or bezafibrate: SHAM-SC, SHAM-HF, SHAM-HF-Bz, OVX-SC, OVX-HF and OVX-HF-Bz. After treatment of 5 weeks, the pancreas was removed and analyzed by morphometry, immunostaining and biochimical assay.

Results: OVX groups showed atrophied uterus compared to the SHAM groups, ensuring the success of surgically-induced menopause. Analyzing the effects of OVX and HF, the SHAM-HF and OVX-HF mice showed higher fasting glucose, plasma insulin, and HOMA-IR; increased body mass, islet hypertrophy, β-cells mass, and insulin immunostain; and decreased GLUT2 immunostain. Bezafibrate treatment reduced body mass, plasma insulin and HOMA-IR, and prevented islet hypertrophy.

**Table 1** Statistics results in C57BL/6 mice.
	Groups
Parameters	SHAM			OVX
Food intake (g)/day per mouse	2.27±0.03	1.94±0.04a	1.95±0.04 a	2.21±0.04	1.91±0.03d	1.89±0.04d
Body mass at 18 week (g)	21.90±0.34	23.32±0.71	23.39±0.43	23.19±0.49	29.95±0.92bd	26.52±0.53cde
Uterus mass (g)	0.14±0.01	0.14±0.02	0.13±0.02	0.03±0.01a	0.04±0.01b	0.03±0.01c
Basal glucose (mmol/l)	5.63±0.19	6.30±0.32	7.14±0.01a	6.71±0.10	8.01±0.37bd	8.21±0.30d
OGTT, AUC	1518±568	1561±1390	1902±593	1719±793	2429±1403bd	2294±983d
Serum insulin (μUI/l)	11.86±0.76	10.23±0.77	9.91±0.77	15.07±1.08	19.37±1.19bd	9.70±0.80de
HOMA-IR	3.06±0.22	3.00±0.24	3.14±0.25	4.47±0.27	7.18±0.50bd	3.57±0.36e
Pancreas mass (g)	253.6±0.01	266.5±0.01	222.2±0.01	261.5±0.01	318.2±0.01bd	282.0±0.01
Vv islet (%)	9.36±0.54	14.05±0.60a	8.10±0.66b	11.36±0.83	14.19±0.79	10.34±0.70e
Islet mass (mg)	24.30±1.48	38.32±1.84a	19.21±1.71b	32.13±2.76 a	44.02±2.45d	29.16±2.08ce
b-cell mass (mg)	17.51±2.18	24.54±2.06	10.37±2.00b	20.54±2.27a	20.63±2.55e	20.63±2.55e

Conclusion: The model of ovariectomy associated with HFD accentuated the effects of menopause, leading to the development of IR. Bezafibrate treatment reduces body mass, and also reduces plasma insulin and pancreatic islet hypertrophy in mice fed HFD.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.

Endocrine Abstracts

P1194