Ovariectomy enhances female rats' susceptibility to metabolic, oxidative, and heat shock response effects induced by a high-fat diet and fine particulate matter.

Obesity and exposure to fine particulate matter (air pollutant PM2.5) are important risk factors for metabolic and cardiovascular diseases. They are also related to early menopause. The reduction of 17β-estradiol (E2) levels during female climacteric, marked by menopause, is of significant concern because of its imminent influence on metabolism, redox and inflammatory status. This complex homeostasis-threatening scenario may induce a heat shock response (HSR) in cells, enhancing the expression of the 70 kDa heat shock protein (HSP70). A failure in this mechanism could predispose women to cardiovascular diseases. In this study, we evaluated if the climacteric could represent an additional risk among obese rats exposed to PM2.5 by worsening lipid, oxidative, and inflammatory parameters and HSP70 in cardiac tissue. We induced obesity in female Wistar rats using a high-fat diet (HFD) (58.3% as fats) and exposed them to 50 μL of saline 0.9% (control, n = 15) or 250 μg residual oil fly ash (ROFA, the inorganic portion of PM2.5) (polluted, n = 15) by intranasal instillation, 5 days/w for 12 weeks. At the 12th week, we subdivided these animals into four groups: control (n = 6), OVX (n = 9), polluted (n = 6) and polluted + OVX (n = 9). OVX and polluted + OVX were submitted to a bilateral ovariectomy (OVX), a surgical model for menopause, while control and polluted received a false surgery (sham). ROFA exposure and HFD consumption were continued for 12 additional weeks, after which the animals were euthanized. ROFA enhanced the susceptibility to ovariectomy-induced dyslipidemia, while ovariectomy predisposed female rats to the ROFA-induced decrease of cardiac iHSP70 expression. Ovariectomy also decreased the IL-6 levels and IL-6/IL-10 in obese animals, reinforcing a metabolic impairment and a failure to respond to unfavorable conditions. Our results support the hypothesis that obese ovariectomized animals are predisposed to a metabolic worsening under polluted conditions and are at higher risk of cardiovascular diseases.