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: Eun-Kyung Choi, Hyun-Jung Park, Ok-Joo Sul, Monisha Rajasekaran, Rina Yu, Hye-Seon Choi
• Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab) Vol. 308 Issue 8 Pg. E621-30 (Apr 15 2015) ISSN: 1522-1555 [Electronic] United States
• PMID: 25714672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Antimetabolites
• Membrane Proteins
• Organometallic Compounds
• Prodrugs
• Reactive Oxygen Species
• Receptors, Cytoplasmic and Nuclear
• tricarbonyldichlororuthenium (II) dimer
• Carbon Monoxide
• Heme Oxygenase-1
• Hmox1 protein, mouse
• Guanylate Cyclase
• Soluble Guanylyl Cyclase
• Cyclic GMP

Topics

• Adipose Tissue, White (drug effects, immunology, metabolism, pathology)
• Adiposity (drug effects)
• Aging
• Animals
• Antimetabolites (pharmacology)
• Carbon Monoxide (pharmacology)
• Cells, Cultured
• Cyclic GMP (agonists, metabolism)
• Female
• Guanylate Cyclase (antagonists & inhibitors, genetics, metabolism)
• Heme Oxygenase-1 (antagonists & inhibitors, genetics, metabolism)
• Injections, Intraperitoneal
• Insulin Resistance
• Macrophages (drug effects, immunology, metabolism)
• Membrane Proteins (antagonists & inhibitors, genetics, metabolism)
• Mice, Inbred C57BL
• Organometallic Compounds (administration & dosage, pharmacology, therapeutic use)
• Ovariectomy (adverse effects)
• Panniculitis (immunology, metabolism, pathology, prevention & control)
• Prodrugs (administration & dosage, pharmacology, therapeutic use)
• RNA Interference
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Receptors, Cytoplasmic and Nuclear (antagonists & inhibitors, genetics, metabolism)
• Soluble Guanylyl Cyclase
• Specific Pathogen-Free Organisms