title: Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema.
abstract: Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE2, we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component.
authors.affiliation: Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki, Ibaraki 300-0395, Japan. Electronic address: tak1924@tokyo-med.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Comprehensive and Internal Medicine, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishi-ogu, Arakawa-ku 116-8567, 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: basuketto454@yahoo.co.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: fraser@tokyo-med.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Itoh
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: The First Department of Medicine, Tokyo Women's Medical University, 8-1 Kawata-cho, Shinjyuku-ku 162-8666, Japan. Electronic address: nagai.atsushi@twmu.ac.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: D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000098:blood supply* / Q000473:pathology; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C499423:9-deoxy-9-chloro-15-deoxy-16-hydroxy-17,17-trimethylene-19,20-didehydroprostaglandin E2; D058307:Receptors, Prostaglandin E, EP2 Subtype; D042461:Vascular Endothelial Growth Factor A; D010196:Pancreatic Elastase; D015232:Dinoprostone
keywords: Adipogenesis; Angiogenesis; COPD; Cachexia; EP2 receptor agonist; Pulmonary emphysema