title: Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis.
abstract: Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Gómez-SanMiguel
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gomez-Moreira
authors.affiliation: Department of Basic Sciences in Health, Faculty of Health Sciences, Rey Juan Carlos University, Madrid, Spain.
authors.forename: María Paz
authors.initials: MP
authors.lastname: Nieto-Bona
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Galaz
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and.
authors.forename: Maria Ángeles
authors.initials: MÁ
authors.lastname: Villanúa
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Martín
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain; and ALC@ucm.es.
authors.forename: Asunción
authors.initials: A
authors.lastname: López-Calderón
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000068759:Formoterol Fumarate / Q000008:administration & dosage*; D008297:Male; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000893:Anti-Inflammatory Agents; D018006:Myogenic Regulatory Factors; D000068759:Formoterol Fumarate
keywords: adjuvant-arthritis; cachexia; insulin-like growth factor-binding protein-3; myogenin; β2-adrenoreceptor