title: Fenofibrate administration to arthritic rats increases adiponectin and leptin and prevents oxidative muscle wasting.
abstract: Chronic inflammation induces skeletal muscle wasting and cachexia. In arthritic rats, fenofibrate, a peroxisome proliferator-activated receptor α (PPARα (PPARA)) agonist, reduces wasting of gastrocnemius, a predominantly glycolytic muscle, by decreasing atrogenes and myostatin. Considering that fenofibrate increases fatty acid oxidation, the aim of this study was to elucidate whether fenofibrate is able to prevent the effect of arthritis on serum adipokines and on soleus, a type I muscle in which oxidative metabolism is the dominant source of energy. Arthritis was induced by injection of Freund's adjuvant. Four days after the injection, control and arthritic rats were gavaged daily with fenofibrate (300 mg/kg bw) or vehicle over 12 days. Arthritis decreased serum leptin, adiponectin, and insulin (P<0.01) but not resistin levels. In arthritic rats, fenofibrate administration increased serum concentrations of leptin and adiponectin. Arthritis decreased soleus weight, cross-sectional area, fiber size, and its Ppar α mRNA expression. In arthritic rats, fenofibrate increased soleus weight, fiber size, and Ppar α expression and prevented the increase in Murf1 mRNA. Fenofibrate decreased myostatin, whereas it increased MyoD (Myod1) and myogenin expressions in the soleus of control and arthritic rats. These data suggest that in oxidative muscle, fenofibrate treatment is able to prevent arthritis-induced muscle wasting by decreasing Murf1 and myostatin expression and also by increasing the myogenic regulatory factors, MyoD and myogenin. Taking into account the beneficial action of adiponectin on muscle wasting and the correlation between adiponectin and soleus mass, part of the anticachectic action of fenofibrate may be mediated through stimulation of adiponectin secretion.
authors.affiliation: Department of Physiology, Faculty of Medicine Complutense University of Madrid 28040, Madrid Spain.
authors.forename: Estíbaliz
authors.initials: E
authors.lastname: Castillero
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Martín
authors.forename: Maria Paz
authors.initials: MP
authors.lastname: Nieto-Bona
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Galaz
authors.forename: María
authors.initials: M
authors.lastname: López-Menduiña
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Villanúa
authors.forename: Asunción
authors.initials: A
authors.lastname: López-Calderón
keywords: Insulin; Murf1; MyoD; PPAR alpha; adiponectin; adjuvant-induced arthritis; fenofibrate; leptin; myogenin; myostatin; oxidative muscle