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Adverse association between obesity and menopause in mice treated with bezafibrate, a pan peroxisome proliferator–activated receptor agonist

da Silva Faria, Tatiane BSc, PhD; Correia-Junior, Antonio Ludgero BSc, MSc; dos Anjos, Thabata Lessa MD; Aguila, Marcia Barbosa RD, PhD; Mandarim-de-Lacerda, Carlos Alberto MD, PhD

doi: 10.1097/GME.0b013e31828f5e3c
Original Articles

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.

From the Laboratory of Morphometry, Metabolism, and Cardiovascular Disease, Biomedical Center, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Received December 5, 2012; revised and accepted February 26, 2013.

Funding/support: This study was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico ( and Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Carlos Alberto Mandarim-de-Lacerda, MD, PhD, Laboratorio de Morfometria, Metabolismo e Doença Cardiovascular, Centro Biomedico, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro, 87, fds, Rio de Janeiro 20551-030, RJ, Brazil. E-mail:

© 2013 by The North American Menopause Society.