Changes in central and peripheral inflammatory responses to lipopolysaccharide in ovariectomized female rats

Obesity leads to increases in inflammatory responses in a site-specific manner. Ovariectomized animals, usually used as menopause models, exhibit obesity; however, their inflammatory responses have not been fully examined. In the present study, we investigated whether ovariectomy had site-specific effects on inflammatory responses. First, fever and anorectic responses to systemic injections of lipopolysaccharide (LPS) (500μg/kg, i.p.) were compared between ovariectomized rats (OVX) and sham-operated female rats (Sham). Inflammatory cytokines at the central and peripheral levels were also compared under saline-injected and LPS-injected conditions. Body weight in OVX was significantly higher than in Sham. The anorectic responses (reduction of body weight and food intake) to LPS were higher in OVX than in Sham. In the hypothalamus, all of the examined cytokine (IL-1β, TNF-α and IL-6) mRNA levels in OVX were higher than in Sham under the LPS-injected condition. On the other hand, in serum and adipose tissue, only IL-6, not IL-1β and TNF-α, levels in OVX were significantly higher than those in Sham under the LPS-injected condition. Second, responses to central (intracerebroventricular) injections of LPS (500ng) were compared between OVX and Sham. The result was that the fever response in OVX was more evident than in Sham. Finally, responses to systemic injections of LPS (500μg/kg, i.p.) were compared between OVX (OVX-oil) and OVX with estradiol (E) and progesterone (P) supplementation (OVX-EP). The anorectic responses and hypothalamic cytokine mRNA levels under LPS-injected condition were not different between OVX-oil and OVX-EP. These results indicate that ovariectomy enhances inflammatory responses, especially at the central level compared with the peripheral level. As supplementation of E and P could not attenuate the anorectic and cytokine responses to LPS, the deficiency of gonadal steroids might not be directly involved in the increase of inflammatory responses in OVX.