Promotion of adipogenesis by an EP2 receptor agonist via stimulation of angiogenesis in pulmonary emphysema

• Published in: Prostaglandins & other lipid mediators 2014-08, Vol.112, p.9-15
• Main Authors: Tsuji, Takao, Yamaguchi, Kazuhiro, Kikuchi, Ryota, Itoh, Masayuki, Nakamura, Hiroyuki, Nagai, Atsushi, Aoshiba, Kazutetsu
• Format: Article
• Language: English
• Subjects: Adipogenesis; Adipogenesis - drug effects; Adipose Tissue - blood supply; Adipose Tissue - pathology; Angiogenesis; Animals; Cachexia; COPD; Dinoprostone - administration & dosage; Dinoprostone - analogs & derivatives; Disease Models, Animal; EP2 receptor agonist; Injections, Intraperitoneal; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic - drug effects; Pancreatic Elastase; Pulmonary emphysema; Pulmonary Emphysema - chemically induced; Pulmonary Emphysema - pathology; Pulmonary Emphysema - physiopathology; Receptors, Prostaglandin E, EP2 Subtype - agonists; Vascular Endothelial Growth Factor A - biosynthesis
• ISSN: 1098-8823
• DOI: 10.1016/j.prostaglandins.2014.05.003

•Body weight loss and adipose tissue wasting are common in patients with COPD.•Adipose angiogenesis is a key mediator of adipogenesis.•EP2 receptor agonist can stimulate adipose angiogenesis via VEGF, and adipogenesis.•EP2 receptor agonist may serve as a therapeutic option in cachexic COPD patients. 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.