Oxidative Phenotype Protects Myofibers from Pathological Insults Induced by Chronic Heart Failure in Mice

Abstract

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.

Muscle oxidative capacity during IL-6-dependent cancer cachexia

“…Although chronic inflammation and insulin resistance are associated with many types of cachexia, the diverse chronic diseases that induce skeletal muscle catabolism may have both common and unique regulatory mechanisms related to the wasting process. There is evidence that muscle phenotype differentially regulates muscle catabolism with many wasting diseases (30), with primarily fast glycolytic muscle mass being more susceptible to loss compared with slow oxidative muscle (8,32,59). These results differ from disuse-induced muscle atrophy (i.e., bed-rest, spaceflight) where slow-oxidative muscle fibers initially undergo a greater atrophy (12).…”

“…An important question related to muscle wasting with several disease states is how a muscle's capacity for oxidative metabolism influences its catabolic susceptibility (32,59). We report here that the reduction of muscle mass in our tumorbearing mice is associated with a loss of overall muscle oxidative capacity in both primarily red and white hindlimb skeletal muscle.…”

“…However, the implications of this altered metabolic capacity in the overall wasting process remain poorly defined. Skeletal muscle's capacity for oxidative metabolism has been implicated as a factor for determining a muscle's sensitivity to inflammatory, metabolic, and agingrelated challenges (4,19,32,59). To our knowledge, this is the first study to report that during IL-6-dependent cancer cachexia, skeletal muscle oxidative capacity is reduced, and this occurs in both glycolytic and oxidative skeletal muscles.…”

Réhabilitation respiratoire dans la broncho-pneumopathie chronique obstructive (BPCO) : l’androgénothérapie, pourquoi ? Pour qui ? Comment ?

“…En effet, les médiateurs du catabolisme protéique sont les cytokines pro-inflammatoires : tumor necrosis factor-α (TNF-␣), interleukine-1 (IL-1), interleukine-6 (IL-6), interleukine-8 (IL-8), interféron-y (INF-y). Cependant, le maintien d'un phénotype musculaire oxydatif pourrait protéger les fibres musculaires des agressions, comme cela est démontré dans des modèles d'insuffisance cardiaque chronique chez la souris [28,39]. Par conséquent, préserver la masse et la fonction musculaires en maintenant le métabolisme mitochondrial oxydatif est un point clé de la prise en charge du patient BPCO.…”

Protein tyrosine nitration in chronic intramuscular parasitism: immunohistochemical evaluation of relationships between nitration, and fiber type-specific responses to infection

“…51 More recent investigations suggest that the catabolic response of muscle to a given pathological stimulus as a function of fiber type involvement is complex. Where the specificity of impact of disease processes was examined in regard to affected fiber types, Li et al 52 indicated that fast glycolytic Type IIb fibers were selectively atrophied in skeletal muscle of patients with chronic heart failure. This response also was observed in studies where subjects with left ventricular dysfunction presented Type IIb-specific fiber atrophy.…”