title: Ghrelin ameliorates catabolic conditions and respiratory dysfunction in a chronic obstructive pulmonary disease model of chronic cigarette smoke-exposed rats.
abstract: Cigarette smoking, which is a well-known major risk factor for chronic obstructive pulmonary disease (COPD), causes both pulmonary and extrapulmonary abnormalities. Ghrelin is a gastric peptide that regulates energy homeostasis. In the present study, we investigated the effects of ghrelin on the catabolic changes, respiratory function and emphysema in an animal model of COPD induced by chronic exposure to cigarette smoke. Rats were exposed to cigarette smoke, and they were administered human ghrelin (0.1 or 1 mg/kg, subcutaneous, twice daily) for 12 weeks. Compared with air-exposed rats, body weight gain, food intake, food efficiency, tidal volume, peak expiratory flow rate, and forced expiratory volume at 100 ms were significantly lower, while functional residual capacity, lung capacity, and neutrophils in bronchoalveolar lavage fluid were significantly higher in cigarette smoke-exposed rats. These indicated that the systemic abnormalities associated with COPD developed after the exposure to cigarette smoke. Ghrelin significantly and dose-dependently increased the body weight gain and food efficiency in cigarette smoke-exposed rats. In ghrelin-treated rats, skeletal muscle strength, which tended to be lowered by cigarette smoke exposure, was improved. Ghrelin ameliorated respiratory function and emphysema in a dose-dependent manner, but did not inhibit the increase in neutrophils in the bronchoalveolar lavage fluid. The respiratory functional parameters and lung capacity were significantly correlated with body weight gain. These results suggest that ghrelin inhibited the development of the catabolic changes, respiratory dysfunction, and emphysema that were induced by cigarette smoke exposure in rats, at least in part, through the amelioration of nutritional status.
authors.affiliation: Faculty of Pharmacology I, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1, Shimotsuke, Tochigi 329-0498, Japan. Electronic address: kamiide.yoshiyuki.g6@asubio.co.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kamiide
authors.affiliation: Faculty of Pharmacology I, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: inomata.norio.d5@asubio.co.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Inomata
authors.affiliation: Faculty of Pharmacology I, Asubio Pharma Co., Ltd., 6-4-3, Minatojima-Minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: furuya.mayumi.cs@asubio.co.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Furuya
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, 3311-1, Shimotsuke, Tochigi 329-0498, Japan. Electronic address: tyada@jichi.ac.jp.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002097:C-Reactive Protein / Q000032:analysis; D002452:Cell Count; D004195:Disease Models, Animal; D005541:Forced Expiratory Volume; D005552:Forelimb; D054439:Ghrelin / Q000494:pharmacology* / Q000627:therapeutic use*; D018737:Hand Strength; D020738:Leptin / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D010366:Peak Expiratory Flow Rate; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects; D013990:Tidal Volume; D014026:Nicotiana
chemical_list: D054439:Ghrelin; D020738:Leptin; D012906:Smoke; D002097:C-Reactive Protein
keywords: Cachexia; Chronic obstructive pulmonary disease; Cigarette smoke; Ghrelin; Human ghrelin (PubChem CID: 71728433); Rat