Gómez-SanMiguel AB, Gomez-Moreira C, Nieto-Bona MP, Fernández-Galaz C, Villanúa MÁ, Martín AI, López-Calderón A. Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis. Am J Physiol Endocrinol Metab 310: E925-E937, 2016; doi:10.1152 doi:10. /ajpendo.00503.2015 arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. ␤2adrenergic receptor agonists are powerful anabolic agents that trigger

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... 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 ␤2-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 g/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, crosssectional 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-B(p65) activation, TNF␣, 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-B(p65)/TNF pathway, and IGFBP-3. cachexia; adjuvant-arthritis; ␤2-adrenoreceptor; myogenin; insulinlike growth factor-binding protein-3 CHRONIC INFLAMMATORY ILLNESSES such as cancer, sepsis, and obstructive pulmonary disease are associated with a decrease in body weight and cachexia. Similarly, patients with rheumatoid arthritis have rheumatoid cachexia, which increases morbidity and mortality (33). Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that induces inflammatory cachexia. On days 10 and 11 after adjuvant injection, rats stop gaining body weight and develop chronic inflammation, polyarthritis, anorexia, and cachexia due to whole body wasting, including muscle and fat tissue loss (6, 33). Skeletal muscle