title: Carbon monoxide reverses adipose tissue inflammation and insulin resistance upon loss of ovarian function.
abstract: We hypothesized that carbon monoxide (CO) might suppress chronic inflammation, which led to metabolic disturbances. Ovariectomy (OVX) was performed in mice to mimic chronic inflammation secondary to loss of ovarian function. OVX increased fat mass and the infiltration of highly inflammatory CD11c cells into adipose tissue (AT), resulting in a disturbance of glucose metabolism. Treatment of CO attenuated these; CO decreased recruitment of CD11c-expressing cells in AT and reduced expression of CD11c in bone marrow-derived macrophages, protecting them from M1 polarization. Upregulated cGMP and decreased reactive oxygen species were responsible for the inhibitory activity of CO on CD11c expression; knockdown of soluble guanylate cyclase or heme oxygenase-1 using small interfering RNAs reduced this inhibition substantially. Improved OVX-induced insulin resistance (IR) by CO was highly associated with its activity to attenuate AT inflammation. Our results suggest a therapeutic value of CO to treat postmenopausal IR by reducing AT inflammation.
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, South Korea; and.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, South Korea; and.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, South Korea; and.
authors.forename: Ok-Joo
authors.initials: OJ
authors.lastname: Sul
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, South Korea; and.
authors.forename: Monisha
authors.initials: M
authors.lastname: Rajasekaran
authors.affiliation: Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
authors.forename: Rina
authors.initials: R
authors.lastname: Yu
authors.affiliation: Department of Biological Sciences, University of Ulsan, Ulsan, South Korea; and hschoi@mail.ulsan.ac.kr.
authors.forename: Hye-Seon
authors.initials: HS
authors.lastname: Choi
mesh_terms: D052436:Adipose Tissue, White / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050154:Adiposity / Q000187:drug effects; D000375:Aging; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000494:pharmacology*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000819:agonists / Q000378:metabolism; D005260:Female; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007333:Insulin Resistance; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010052:Ovariectomy / Q000009:adverse effects; D015434:Panniculitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011355:Prodrugs / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013047:Specific Pathogen-Free Organisms
chemical_list: D000963:Antimetabolites; D008565:Membrane Proteins; D009942:Organometallic Compounds; D011355:Prodrugs; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: CD11c; adipose tissue inflammation; carbon monoxide; insulin resistance; loss of ovarian function