TNFα receptor genotype influences smoking-induced muscle-fibre-type shift and atrophy in mice

Abstract

Systemic manifestations of chronic obstructive pulmonary disease (COPD) include muscle wasting, and tumour necrosis factor alpha (TNFalpha) could represent a major inducer of these processes. We studied skeletal muscle histology in a murine model of cigarette smoke (CS)-induced COPD, comparing mice with different TNFalpha receptor genotypes. Muscles from hind limbs of wild type (WT), TNFalpha receptor 1 knockout (TNF alpha R1KO) and TNF alpha R2KO mice were prepared and weighed. The lower body weight, which was observed in CS-exposed WT and TNF alpha R1KO mice, was paralleled by reduced weights of gastrocnemius and biceps femoris muscle. The gastrocnemius muscle was evaluated for muscle fibre apoptosis and atrophy, and fibre-type distribution. CS-induced apoptosis was observed in all genotypes, while a significant reduction of cross-sectional areas of myofibres was present only in TNF alpha R2KO mice. A CS-induced fibre-type shift from the IIa to the IIb phenotype was observed in WT mice, an increase of muscle-fibre-type IIx was noticed in CS-exposed TNF alpha R2KO mice. Our data suggest that the skeletal muscle manifestations associated with this murine COPD model are under complex regulation by both TNFalpha receptors, but that TNF alpha R2 may be the most important determinant for the outcome of CS-induced myofibre apoptosis.

Interaction between Physical Activity and Smoking on Lung, Muscle, and Bone in Mice

“…As expected, smoking caused emphysema (23), reduced food intake (24,25) and lowered body weight (23,(26)(27)(28)(29). While reduced food intake could only partially explain the lowered body weight, as previously reported (24), loss of fat mass (28) and reduced lean mass and body growth also contribute to body weight loss.…”

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

“…Cigarette smoking is unlikely to be the main mechanism involved in limb muscle dysfunction in COPD because, in several studies, patients and control subjects were matched for smoking history. However, smoking by itself has some effects on muscle biology (416)(417)(418)(419), and it is possible that it may predispose patients to the development of limb muscle dysfunction. Smoking by itself may be associated with muscle atrophy and weakness in otherwise healthy subjects (4,236,248).…”

Long-term nose-only cigarette smoke exposure induces emphysema and mild skeletal muscle dysfunction in mice

“…To explore the mechanisms that contribute to muscle dysfunction in COPD, skeletal muscle fiber changes and muscle contractile properties need to be determined. Some studies investigated peripheral skeletal muscle fiber-type changes and enzyme content in elastase-induced emphysema in hamsters (Mattson and Martin, 2005; Mattson et al, 2008) and in CS-induced emphysema models by whole-body exposure (Ardite et al, 2006; De Paepe et al, 2008; Tang et al, 2010; Barreiro et al, 2010), but so far no studies are available exploring contractile properties and histological changes in a nose-only CS exposure model. Theoretically, the latter model is superior for such a purpose because it avoids systemic effects by the uptake of tar substances or nicotine through the skin.…”