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Changes in central and peripheral inflammatory responses to lipopolysaccharide in ovariectomized female rats
Affiliation:1. INRA, Nutrition et neurobiologie intégrée, UMR 1286, 33076 Bordeaux, France;2. Univ. Bordeaux, Nutrition et neurobiologie intégrée, UMR 1286, 33076 Bordeaux, France;1. Research Fellow, Oral and Maxillofacial Surgery/Dental Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA;2. Associate Clinical Professor, Department of Orthopaedic Surgery, UCLA Medical Center, Los Angeles, CA;3. Research Fellow, Oral and Maxillofacial Surgery/Dental Service, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA;4. Director, Research Fellowship and Inpatient Oral and Maxillofacial Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles; Instructor, Department of Oral and Maxillofacial Surgery, UCLA School of Dentistry, Los Angeles, CA;6. Professor Emeritus, Division of Advanced Prosthodontics, UCLA School of Dentistry, Los Angeles, CA;5. Director, Graduate Medical Education, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles; Professor in Residence, Department of Oral and Maxillofacial Surgery, UCLA School of Dentistry, Los Angeles; Director, Quality Assurance, Hospital Dental Service, Ronald Reagan UCLA Medical Center, Los Angeles, CA;1. Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Sciences, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK;2. CGAT, MRC Weatherall Institute of Molecular Medicine Centre for Computational Biology, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK;2. USDA Agricultural Research Service, National Animal Disease Center, Ames, IA 50010;3. University of Arkansas, Department of Poultry Science, Fayetteville 72701;4. Applied Animal Biotechnology Laboratories, School of Animal Sciences, Louisiana Agricultural Experiment Station, Louisiana State University Agricultural Center, Louisiana State University, Baton Rouge 70803;1. Department of Medical Entomology and Vector Control, School of Public Health, Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran;2. Department of Parasitology, School of Public Health, Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran;3. Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, P.O. Box 14155-6446, Tehran, Iran
Abstract: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) (500 μg/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 (500 ng) 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 (500 μg/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.
Keywords:Ovariectomy  Obesity  IL-6  IL-1β  TNF-α
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