title: Improvement of metabolic disorders by an EP2receptor agonist via restoration of the subcutaneous adipose tissue in pulmonary emphysema.
abstract: Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue.
authors.affiliation: Institute of Geriatrics, Tokyo Women's Medical University, 2-15-1 Shibuya, Shibuya, Tokyo 150-0002, Japan; Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan. Electronic address: tsuji.takao@twmu.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Division of Comprehensive Sleep Medicine, Tokyo Women's Medical University, 8-1,Kawada-cho, Sinjuku, Tokyo 162-8666, Japan. Electronic address: yamaguc@sirius.ocn.ne.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan. Electronic address: reo1129@tokyo-med.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kikuchi
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan. Electronic address: hiroyuki@tokyo-med.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Institute of Geriatrics, Tokyo Women's Medical University, 2-15-1 Shibuya, Shibuya, Tokyo 150-0002, Japan. Electronic address: misaka.ryoichi@twmu.ac.jp.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Misaka
authors.affiliation: Reserch Institute for Respiratory Diseases, Shin-yurigaoka GeneralHospital, 255 Asou, Kawasaki, Kanagawa 215-0026, Japan. Electronic address: atsushi.nagai@mt.strins.or.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nagai
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan. Electronic address: kaoshiba@tokyo-med.ac.jp.
authors.forename: Kazutetsu
authors.initials: K
authors.lastname: Aoshiba
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D008659:Metabolic Diseases / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011656:Pulmonary Emphysema / Q000150:complications*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists*; D050151:Subcutaneous Fat / Q000187:drug effects* / Q000473:pathology
chemical_list: C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D058307:Receptors, Prostaglandin E, EP2 Subtype; D005947:Glucose; D015232:Dinoprostone
keywords: COPD; Cachexia; EP2 receptor agonist; Metabolic disorders; Pulmonary emphysema; Subcutaneous adipose tissue