Muscle Metabolic Modulation by Chronic Hypoxia

De Palma et al. published a research paper in which they describe the effect of chronic hypoxia on rat skeletal muscle metabolism by means of a comparative proteomic analysis (J. Proteome Res. 2007, 6(5), 1974-1984). For this, relatively young animals were used. In our communication, we note that, based on other literature, it is likely that the adaptive response of skeletal muscle to hypoxia attenuates with age. Keywords: skeletal muscles * hypoxia * muscle fiber types * energy metabolism * hypoxia inducible factor 1alpha (HIF1alpha)

Chronic obstructive pulmonary disease patient journey: hospitalizations as window of opportunity for extra-pulmonary intervention.

PURPOSE OF REVIEW: Hospitalizations due to exacerbation of chronic pulmonary disease (COPD) are a major burden for patient and healthcare Extra-pulmonary needs and resulting interventions are poorly FINDINGS: COPD induces nutritional issues, body composition changes and patient exercise capacity. The COPD patient journey can be accelerated exacerbations during which disease-related detrimental factors such as inflammation, hypoxia, inactivity, and glucocorticosteroid treatment intensify, which acutely and often irreversibly worsens patient Specific needs during exacerbations reach beyond the respiratory system, clinicians should comprehensively evaluate patients and identify potent feasible metabolic and anabolic intervention targets. General and nutritional support appear feasible and with potential to cover for the bodily requirements during exacerbation. Adjunctive physical exercise or neuromuscular electrical stimulation may prevent the muscle loss. Hospitalizations should be considered as a window of opportunity for patient assessment and implementation of tailored extra-pulmonary strategies with long-term implications. Nutritional assessment and well as physical exercise appear promising but should be investigated in adequately designed and conducted trials

Physical activity, nutritional status and systemic inflammation in COPD

status: publishe

Hypoxia and muscle maintenance regulation: implications for chronic respiratory disease

PURPOSE OF REVIEW: Muscle wasting and impaired muscle oxidative metabolism are common extrapulmonary features of chronic respiratory failure (CRF) that significantly increase disease burden. This review aims to address the question whether hypoxia, an obvious consequence of this disease, actually plays a causal role in these muscle impairments. RECENT FINDINGS: In experimental models, a causal role for hypoxia in muscle atrophy and metabolic impairments has clearly been shown. Although the hypoxia-inducible factors and nuclear factor kappa B are putative mediators of these hypoxia-induced alterations, their true involvement remains to be proven. Molecular signatures of disrupted regulation of muscle mass and oxidative metabolism observed in these experimental models also have been shown in muscles of patients suffering from CRF, suggestive of but not conclusive for a causal role of hypoxia. Therapies, including but not restricted to those aimed at alleviating hypoxia, have been shown to partially but not completely restore muscle mass and oxidative capacity in CRF patients, which may imply an additive effect of nutritional modulation of substrate metabolism. SUMMARY: Although hypoxia clearly affects skeletal muscle maintenance, it remains to be confirmed whether and by which underlying molecular mechanisms hypoxia is causally involved in CRF-related muscle atrophy and impaired oxidative capacity

Cigarette smoke extract induces a phenotypic shift in epithelial cells: involvement of HIF1α in mesenchymal transition

In COPD, matrix remodeling contributes to airflow limitation. Recent evidence suggests that next to fibroblasts, the process of epithelial-mesenchymal transition can contribute to matrix remodeling. CSE has been shown to induce EMT in lung epithelial cells, but the signaling mechanisms involved are largely unknown and subject of this study. EMT was assessed in A549 and BEAS2B cells stimulated with CSE by qPCR, Western blotting and immunofluorescence for epithelial and mesenchymal markers, as were collagen production, cell adhesion and barrier integrity as functional endpoints. Involvement of TGF-beta and HIF1 alpha signaling pathways were investigated. In addition, mouse models were used to examine the effects of CS on hypoxia signaling and of hypoxia per se on mesenchymal expression. CSE induced EMT characteristics in A549 and BEAS2B cells, evidenced by decreased expression of epithelial markers and a concomitant increase in mesenchymal marker expression after CSE exposure. Furthermore cells that underwent EMT showed increased production of collagen, decreased adhesion and disrupted barrier integrity. The induction of EMT was found to be independent of TGF-beta signaling. On the contrary, CS was able to induce hypoxic signaling in A549 and BEAS2B cells as well as in mice lung tissue. Importantly, HIF1 alpha knock-down prevented induction of mesenchymal markers, increased collagen production and decreased adhesion after CSE exposure, data that are in line with the observed induction of mesenchymal marker expression by hypoxia in vitro and in vivo. Together these data provide evidence that both bronchial and alveolar epithelial cells undergo a functional phenotypic shift in response to CSE exposure which can contribute to increased collagen deposition in COPD lungs. Moreover, HIF1 alpha signaling appears to play an important role in this process

Dietary fibre and fatty acids in chronic obstructive pulmonary disease risk and progression: a systematic review.

Dietary intake attracts increasing interest in the risk for and chronic obstructive pulmonary disease (COPD). In particular, dietary fatty acids have drawn specific attention for their immunomodulating The study aimed to review the current evidence on the potential roles of fibre or fatty acid intake in the risk and progression of COPD. Pubmed, Cochrane Collaboration Database and conference databases for original adults addressing the association between fibre or fatty acid intake and terms of risk, lung function and respiratory symptoms were searched. articles were included of which four reported on dietary fibre and five acids. Data of studies could not be pooled because of methodological Greater intake of dietary fibre has been consistently associated with COPD risk, better lung function and reduced respiratory symptoms. associations between fatty acids and COPD are inconsistent. Dietary deserves further attention in developing COPD prevention and managemen