{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T20:57:41Z","timestamp":1782248261553,"version":"3.54.5"},"reference-count":118,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lung foundation Netherlands","award":["5.1.18.232"],"award-info":[{"award-number":["5.1.18.232"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by airflow limitation. Apart from airflow limitation, patients with COPD may also suffer from extra-pulmonary features such as lower limb muscle dysfunction that contribute to an impaired health status. Since the latest statement on lower-limb muscle dysfunction in COPD in 2014, substantial new evidence has emerged with regard to molecular, cellular, and functional mechanisms underlying muscle plasticity. Therefore, this review aims to provide an updated overview of molecular, cellular, and functional mechanisms of lower-limb muscle plasticity in COPD, integrating evidence that has emerged since the 2014 statement on lower limb muscle dysfunction. Additionally, the effects of exercise training on mechanisms of limb muscle dysfunction are explained. From the evidence of the last decade, it can be concluded that limb muscle dysfunction is a multifactorial process driven by both intrinsic alterations and impairments to the muscle as well as extra-pulmonary influences, thereby reinforcing the need for integrated therapeutic strategies.<\/jats:p>","DOI":"10.3390\/cells15030220","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T17:52:38Z","timestamp":1769190758000},"page":"220","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Lower-Limb Muscle Impairments in Patients with COPD: An Overview of the Past Decade"],"prefix":"10.3390","volume":"15","author":[{"given":"Bente","family":"Brauwers","sequence":"first","affiliation":[{"name":"Department of Research and Development, Ciro, 6085 NM Horn, The Netherlands"},{"name":"NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht University, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3822-7430","authenticated-orcid":false,"given":"Martijn A.","family":"Spruit","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Ciro, 6085 NM Horn, The Netherlands"},{"name":"Department of Respiratory Medicine, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits M. E.","family":"Franssen","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Ciro, 6085 NM Horn, The Netherlands"},{"name":"Department of Respiratory Medicine, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 HX Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-1553","authenticated-orcid":false,"given":"Anouk W.","family":"Vaes","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Ciro, 6085 NM Horn, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1910-7695","authenticated-orcid":false,"given":"Felipe V. C.","family":"Machado","sequence":"additional","affiliation":[{"name":"Rehabilitation Research Center (REVAL), Faculty of Rehabilitation Sciences, Hasselt University, 3500 Diepenbeek, Belgium"},{"name":"BIOMED-Biomedical Research Institute, Faculty of Medicine and Life Sciences, Hasselt University, 3500 Diepenbeek, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"ref_1","unstructured":"Global Initiative for Chronic Obstructive Lung Disease (GOLD) (2026). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, GOLD."},{"key":"ref_2","first-page":"438","article-title":"Treatable traits qualifying for nonpharmacological interventions in COPD patients upon first referral to a pulmonologist: The COPD sTRAITosphere","volume":"6","author":"Koolen","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1183\/09031936.00146906","article-title":"Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD","volume":"30","author":"Gosker","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1164\/rccm.200807-1005OC","article-title":"The mitochondrial phenotype of peripheral muscle in chronic obstructive pulmonary disease: Disuse or dysfunction?","volume":"178","author":"Picard","year":"2008","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1183\/09031936.00112408","article-title":"Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients","volume":"33","author":"Godoy","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1183\/09031936.00144106","article-title":"Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD","volume":"30","author":"Remels","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1164\/ajrccm.157.5.9710039","article-title":"Cytochrome oxidase activity and mitochondrial gene expression in skeletal muscle of patients with chronic obstructive pulmonary disease","volume":"157","author":"Sauleda","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1165\/rcmb.2008-0382OC","article-title":"Cellular markers of muscle atrophy in chronic obstructive pulmonary disease","volume":"42","author":"Plant","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1136\/thorax.55.10.848","article-title":"Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD","volume":"55","author":"Maltais","year":"2000","journal-title":"Thorax"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1183\/09031936.00137211","article-title":"Does oxidative stress modulate limb muscle atrophy in severe COPD patients?","volume":"40","author":"Fermoselle","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1164\/ajrccm.159.3.9803049","article-title":"Evidence of skeletal muscle metabolic reserve during whole body exercise in patients with chronic obstructive pulmonary disease","volume":"159","author":"Richardson","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R935","DOI":"10.1152\/ajpregu.00167.2008","article-title":"Organization of metabolic pathways in vastus lateralis of patients with chronic obstructive pulmonary disease","volume":"295","author":"Green","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1152\/japplphysiol.00153.2010","article-title":"Quadriceps metabolism during constant workrate cycling exercise in chronic obstructive pulmonary disease","volume":"110","author":"Saey","year":"2011","journal-title":"J. Appl. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R1142","DOI":"10.1152\/ajpregu.00835.2010","article-title":"Evidence that a higher ATP cost of muscular contraction contributes to the lower mechanical efficiency associated with COPD: Preliminary findings","volume":"300","author":"Layec","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1152\/japplphysiol.00460.2015","article-title":"Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: The potential role of altered skeletal muscle mitochondrial respiration","volume":"119","author":"Gifford","year":"2015","journal-title":"J. Appl. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Attaway, A.H., Lopez, R., Welch, N., Bellar, A., Hatipo\u011flu, U., Zein, J., Engelen, M.P., and Dasarathy, S. (2024). Muscle loss phenotype in COPD is associated with adverse outcomes in the UK Biobank. BMC Pulm. Med., 24.","DOI":"10.1186\/s12890-024-02999-7"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"American Thoracic Society, and European Respiratory Society (1999). Skeletal muscle dysfunction in chronic obstructive pulmonary disease. A statement of the American Thoracic Society and European Respiratory Society. Am. J. Respir. Crit. Care Med., 159, S1\u2013S40.","DOI":"10.1164\/ajrccm.159.supplement_1.15945"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1164\/rccm.201402-0373ST","article-title":"An Official American Thoracic Society\/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease","volume":"189","author":"Maltais","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1164\/rccm.201710-2140CI","article-title":"Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease. What We Know and Can Do for Our Patients","volume":"198","author":"Jaitovich","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1002\/jcsm.12988","article-title":"Involvement of Parkin-mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease-related sarcopenia","volume":"13","author":"Ito","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pomi\u00e8s, P., Blaqui\u00e8re, M., Maury, J., Mercier, J., Gouzi, F., and Hayot, M. (2016). Involvement of the FoxO1\/MuRF1\/Atrogin-1 Signaling Pathway in the Oxidative Stress-Induced Atrophy of Cultured Chronic Obstructive Pulmonary Disease Myotubes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160092"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"637.e1","DOI":"10.1016\/j.jamda.2017.04.016","article-title":"Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients with Sarcopenia","volume":"18","author":"Kneppers","year":"2017","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/jcmm.12390","article-title":"Reduced myotube diameter, atrophic signalling and elevated oxidative stress in cultured satellite cells from COPD patients","volume":"19","author":"Rodriguez","year":"2015","journal-title":"J. Cell Mol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1002\/jcp.30073","article-title":"Deficient muscle regeneration potential in sarcopenic COPD patients: Role of satellite cells","volume":"236","author":"Guitart","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_25","first-page":"772","article-title":"Myostatin\/Smad2\/Smad3 pathway define a differential clinical phenotype in COPD-associated sarcopenia","volume":"11","author":"Guitart","year":"2025","journal-title":"ERJ Open Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1465-9921-15-35","article-title":"Regenerative defect in vastus lateralis muscle of patients with chronic obstructive pulmonary disease","volume":"15","author":"Lemire","year":"2014","journal-title":"Respir. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Th\u00e9riault, M.E., Par\u00e9, M., Maltais, F., and Debigar\u00e9, R. (2012). Satellite cells senescence in limb muscle of severe patients with COPD. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039124"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1152\/japplphysiol.00882.2018","article-title":"Quadriceps miR-542-3p and -5p are elevated in COPD and reduce function by inhibiting ribosomal and protein synthesis","volume":"126","author":"Lee","year":"2019","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hartmann, J.P., Dahl, R.H., Nymand, S., Munch, G.W., Ryrs\u00f8, C.K., Pedersen, B.K., Thaning, P., Mortensen, S.P., Berg, R.M.G., and Iepsen, U.W. (2022). Regulation of the microvasculature during small muscle mass exercise in chronic obstructive pulmonary disease vs. chronic heart failure. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.979359"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E94","DOI":"10.1152\/ajpendo.00462.2016","article-title":"Oxygen delivery and the restoration of the muscle energetic balance following exercise: Implications for delayed muscle recovery in patients with COPD","volume":"313","author":"Layec","year":"2017","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1249\/MSS.0000000000002364","article-title":"Muscle Oxidative Capacity Is Reduced in Both Upper and Lower Limbs in COPD","volume":"52","author":"Adami","year":"2020","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13395-016-0083-9","article-title":"Failed upregulation of TFAM protein and mitochondrial DNA in oxidatively deficient fibers of chronic obstructive pulmonary disease locomotor muscle","volume":"6","author":"Konokhova","year":"2016","journal-title":"Skelet. Muscle"},{"key":"ref_33","first-page":"PA3408","article-title":"Peripheral muscle mitophagy is enhanced in patients with COPD","volume":"48","author":"Leermakers","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1186\/s12931-020-01527-5","article-title":"Mitochondrial dysfunction in airways and quadriceps muscle of patients with chronic obstructive pulmonary disease","volume":"21","author":"Haji","year":"2020","journal-title":"Respir. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1042\/CS20140428","article-title":"Quadriceps muscle weakness and atrophy are associated with a differential epigenetic profile in advanced COPD","volume":"128","author":"Ausin","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9629","DOI":"10.1002\/jcp.26868","article-title":"Oxidative stress regulates autophagy in cultured muscle cells of patients with chronic obstructive pulmonary disease","volume":"233","author":"Gouzi","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1164\/rccm.201304-0732OC","article-title":"Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease","volume":"188","author":"Guo","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_38","first-page":"PA932","article-title":"Systemic inflammation is associated with mitophagy signalling in skeletal muscle of COPD patients","volume":"52","author":"Gosker","year":"2018","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/s12967-018-1405-y","article-title":"Network modules uncover mechanisms of skeletal muscle dysfunction in COPD patients","volume":"16","author":"Cano","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12165","DOI":"10.1038\/s41598-018-29789-6","article-title":"COPD is accompanied by co-ordinated transcriptional perturbation in the quadriceps affecting the mitochondria and extracellular matrix","volume":"8","author":"Thompson","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Snijders, T., Nederveen, J.P., McKay, B.R., Joanisse, S., Verdijk, L.B., van Loon, L.J., and Parise, G. (2015). Satellite cells in human skeletal muscle plasticity. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00283"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1242\/dev.134411","article-title":"Satellite cell depletion prevents fiber hypertrophy in skeletal muscle","volume":"143","author":"Egner","year":"2016","journal-title":"Development"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1378\/chest.11-2144","article-title":"Inflammatory and satellite cells in the quadriceps of patients with COPD and response to resistance training","volume":"142","author":"Menon","year":"2012","journal-title":"Chest"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1183\/23120541.00203-2024","article-title":"Muscle fibre satellite cells are located at a greater distance from capillaries in patients with COPD compared with healthy controls","volume":"10","author":"Betz","year":"2024","journal-title":"ERJ Open Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000333600","article-title":"The longitudinal relation between smoking and muscle strength in healthy adults","volume":"18","author":"Kok","year":"2012","journal-title":"Eur. Addict. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12931-023-02521-3","article-title":"Incident low muscle mass is associated with greater lung disease and lower circulating leptin in a tobacco-exposed longitudinal cohort","volume":"24","author":"Zou","year":"2023","journal-title":"Respir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1097\/HCR.0000000000000400","article-title":"Muscle Dysfunction in Smokers and Patients with mild COPD: A systematic review","volume":"39","author":"Fonseca","year":"2019","journal-title":"J. Cardiopulm. Rehabil. Prev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.clnu.2022.01.015","article-title":"Physical and mental health profile of patients with the early-onset severe COPD phenotype: A cross-sectional analysis","volume":"41","author":"Beijers","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.tips.2006.07.004","article-title":"Brain nicotinic acetylcholine receptors: Native subtypes and their relevance","volume":"27","author":"Gotti","year":"2006","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1146\/annurev.pharmtox.47.120505.105214","article-title":"Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system","volume":"47","author":"Dani","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"McFadden, K.L., Cornier, M.A., and Tregellas, J.R. (2014). The role of alpha-7 nicotinic receptors in food intake behaviors. Front. Psychol., 5.","DOI":"10.3389\/fpsyg.2014.00553"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.neuropharm.2013.04.028","article-title":"Molecules and circuits involved in nicotine addiction: The many faces of smoking","volume":"76","author":"Picciotto","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/npp.2014.177","article-title":"Differential roles of \u03b16\u03b22* and \u03b14\u03b22* neuronal nicotinic receptors in nicotine- and cocaine-conditioned reward in mice","volume":"40","author":"Sanjakdar","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/ntr\/ntz010","article-title":"Nicotinic Acetylcholine Receptor Signaling in the Hypothalamus: Mechanisms Related to Nicotine\u2019s Effects on Food Intake","volume":"22","author":"Calarco","year":"2019","journal-title":"Nicotine Tob. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"807","DOI":"10.2337\/db11-1079","article-title":"Nicotine induces negative energy balance through hypothalamic AMP-activated protein kinase","volume":"61","author":"Whittle","year":"2012","journal-title":"Diabetes"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1164\/rccm.200506-977OC","article-title":"Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight loss","volume":"173","author":"Chen","year":"2006","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1093\/ntr\/nts159","article-title":"Nicotinic regulation of energy homeostasis","volume":"14","author":"Zoli","year":"2012","journal-title":"Nicotine Tob. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1530\/JOE-17-0166","article-title":"Effects of nicotine on homeostatic and hedonic components of food intake","volume":"235","author":"Stojakovic","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1111\/adb.12167","article-title":"Nicotine enhances modulation of food-cue reactivity by leptin and ghrelin in the ventromedial prefrontal cortex","volume":"20","author":"Kroemer","year":"2015","journal-title":"Addict. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.metabol.2006.11.012","article-title":"Differentiation in the short- and long-term effects of smoking on plasma total ghrelin concentrations between male nonsmokers and habitual smokers","volume":"56","author":"Kokkinos","year":"2007","journal-title":"Metabolism"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1159\/000381834","article-title":"Effects of Cigarette Smoking on Plasma Concentration of the Appetite-Regulating Peptide Ghrelin","volume":"66","author":"Koopmann","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.brainres.2003.08.024","article-title":"Effect of nicotine on the expression of leptin and forebrain leptin receptors in the rat","volume":"991","author":"Li","year":"2003","journal-title":"Brain Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1080\/15622975.2019.1671610","article-title":"Higher fasting ghrelin serum levels in active smokers than in former and never-smokers","volume":"21","author":"Wittekind","year":"2020","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"108194","DOI":"10.1016\/j.appet.2025.108194","article-title":"The association of cigarette smoking with appetite, appetite-related hormones and food reward: A matched-pair cohort study","volume":"214","author":"Alruwaili","year":"2025","journal-title":"Appetite"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.euroneuro.2008.02.006","article-title":"Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens","volume":"18","author":"Jerlhag","year":"2008","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1016\/j.celrep.2018.11.026","article-title":"Ghrelin Enhances Food Odor Conditioning in Healthy Humans: An fMRI Study","volume":"25","author":"Han","year":"2018","journal-title":"Cell Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.2174\/138161211795656819","article-title":"Reward circuitry dopaminergic activation regulates food and drug craving behavior","volume":"17","author":"Blum","year":"2011","journal-title":"Curr. Pharm. Des."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.ypmed.2016.08.009","article-title":"The neurobiological and behavioral overlaps of nicotine and food addiction","volume":"92","author":"Criscitelli","year":"2016","journal-title":"Prev. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3945\/an.111.001792","article-title":"Skeletal muscle responses to negative energy balance: Effects of dietary protein","volume":"3","author":"Carbone","year":"2012","journal-title":"Adv. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1164\/rccm.200908-1220OC","article-title":"Cigarette smoke-induced oxidative stress: A role in chronic obstructive pulmonary disease skeletal muscle dysfunction","volume":"182","author":"Barreiro","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1749-6632.2012.06532.x","article-title":"Sarcopenia and smoking: A possible cellular model of cigarette smoke effects on muscle protein breakdown","volume":"1259","author":"Rom","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"E843","DOI":"10.1152\/ajpendo.00301.2007","article-title":"Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle","volume":"293","author":"Petersen","year":"2007","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_73","first-page":"2","article-title":"Effects of Cigarette Smoking on Some Immunological and Hematological Parameters in Male Smokers in Erbil City","volume":"6","author":"Aula","year":"2013","journal-title":"Jordan J. Biol. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"e5512","DOI":"10.1590\/1414-431x20165512","article-title":"Oxidative stress and skeletal muscle dysfunction are present in healthy smokers","volume":"49","author":"Neves","year":"2016","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/S0891-5849(00)00457-3","article-title":"Exhalation of H2O2 and thiobarbituric acid reactive substances (TBARs) by healthy subjects","volume":"30","author":"Nowak","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.4187\/respcare.01809","article-title":"Oxidative stress in COPD patients, smokers, and non-smokers","volume":"57","author":"Tavilani","year":"2012","journal-title":"Respir. Care"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1158\/1055-9965.EPI-05-0210","article-title":"Mitochondrial DNA content increase in response to cigarette smoking","volume":"15","author":"Masayesva","year":"2006","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Henrot, P., Dupin, I., Schilfarth, P., Esteves, P., Blervaque, L., Zysman, M., Gouzi, F., Hayot, M., Pomi\u00e8s, P., and Berger, P. (2023). Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076454"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1513\/pats.200408-039MS","article-title":"Local and Systemic Inflammation in Chronic Obstructive Pulmonary Disease","volume":"2","author":"Wouters","year":"2005","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s00223-016-0185-8","article-title":"The Role of Tumor Necrosis Factor Alpha and TNF Superfamily Members in Bone Damage in Patients with End-Stage Chronic Obstructive Lung Disease Prior to Lung Transplantation","volume":"99","author":"Kochetkova","year":"2016","journal-title":"Calcif. Tissue Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"127S","DOI":"10.1378\/chest.121.5_suppl.127S","article-title":"Systemic Effects in COPD","volume":"121","author":"Wouters","year":"2002","journal-title":"Chest"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.2147\/COPD.S85954","article-title":"Relation between systemic inflammatory markers, peripheral muscle mass, and strength in limb muscles in stable COPD patients","volume":"10","author":"Ferrari","year":"2015","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1183\/09031936.05.00107404","article-title":"Skeletal muscle inflammation and nitric oxide in patients with COPD","volume":"26","author":"Torres","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1136\/thx.2007.078030","article-title":"Cytokine profile in quadriceps muscles of patients with severe COPD","volume":"63","author":"Barreiro","year":"2008","journal-title":"Thorax"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1365-2362.2007.01867.x","article-title":"Markers of inflammation and disuse in vastus lateralis of chronic obstructive pulmonary disease patients","volume":"37","author":"Crul","year":"2007","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1210\/en.2014-1591","article-title":"TNF-\u03b1-Induced NF-\u03baB Activation Stimulates Skeletal Muscle Glycolytic Metabolism Through Activation of HIF-1\u03b1","volume":"156","author":"Remels","year":"2015","journal-title":"Endocrinology"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Turan, N., Kalko, S., Stincone, A., Clarke, K., Sabah, A., Howlett, K., Curnow, S.J., Rodriguez, D.A., Cascante, M., and O\u2019Neill, L. (2011). A Systems Biology Approach Identifies Molecular Networks Defining Skeletal Muscle Abnormalities in Chronic Obstructive Pulmonary Disease. PLoS Comput. Biol., 7.","DOI":"10.1371\/journal.pcbi.1002129"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"R1659","DOI":"10.1152\/ajpregu.00550.2009","article-title":"Downregulation of Akt\/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia","volume":"298","author":"Favier","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s13105-019-00687-3","article-title":"Impact of different methods of induction of cellular hypoxia: Focus on protein homeostasis signaling pathways and morphology of C2C12 skeletal muscle cells differentiated into myotubes","volume":"75","author":"Bensaid","year":"2019","journal-title":"J. Physiol. Biochem."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Debevec, T., Ganse, B., Mittag, U., Eiken, O., Mekjavic, I.B., and Rittweger, J. (2018). Hypoxia Aggravates Inactivity-Related Muscle Wasting. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00494"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1513\/AnnalsATS.202312-1062OC","article-title":"Nocturnal Hypoxemia Is Associated with Sarcopenia in Patients with Chronic Obstructive Pulmonary Disease","volume":"21","author":"Attaway","year":"2024","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1249\/MSS.0000000000003268","article-title":"The Impact of Exercise Training and Supplemental Oxygen on Peripheral Muscles in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial","volume":"55","author":"Hudelmaier","year":"2023","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Balnis, J., Korponay, T.C., and Jaitovich, A. (2020). AMP-Activated Protein Kinase (AMPK) at the Crossroads Between CO2 Retention and Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease (COPD). Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030955"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Csoma, B., Vulpi, M.R., Dragonieri, S., Bentley, A., Felton, T., L\u00e1z\u00e1r, Z., and Bikov, A. (2022). Hypercapnia in COPD: Causes, Consequences, and Therapy. J. Clin. Med., 11.","DOI":"10.3390\/jcm11113180"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e70079","DOI":"10.1111\/apha.70079","article-title":"Mitochondrial Dysfunction and Defects in Mitochondrial Adaptation to Exercise Training in the Muscle of Patients with COPD: Disease Versus Disuse","volume":"241","author":"Abdellaoui","year":"2025","journal-title":"Acta Physiol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1152\/japplphysiol.00788.2017","article-title":"Altered skeletal muscle mitochondrial phenotype in COPD: Disease vs. disuse","volume":"124","author":"Gifford","year":"2018","journal-title":"J. Appl. Physiol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"15007","DOI":"10.1038\/s41598-018-33471-2","article-title":"Molecular signalling towards mitochondrial breakdown is enhanced in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD)","volume":"8","author":"Leermakers","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.2147\/COPD.S179609","article-title":"Prevalence of malnutrition in COPD and its relationship with the parameters related to disease severity","volume":"13","author":"Mete","year":"2018","journal-title":"Int. J. Chron. Obs. Pulmon. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1038\/s41430-020-0623-6","article-title":"Prevalence of sarcopenia and malnutrition during acute exacerbation of COPD and after 6 months recovery","volume":"74","author":"Perrot","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Tomita, M., Uchida, M., Imaizumi, Y., Monji, M., Tokushima, E., and Kawashima, M. (2022). The Relationship of Energy Malnutrition, Skeletal Muscle and Physical Functional Performance in Patients with Stable Chronic Obstructive Pulmonary Disease. Nutrients, 14.","DOI":"10.3390\/nu14132596"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2147\/COPD.S458102","article-title":"Vitamin D Status and Longitudinal Changes in Body Composition in Patients with Chronic Obstructive Pulmonary Disease\u2014A Prospective Observational Study","volume":"19","author":"Minter","year":"2024","journal-title":"Int. J. Chron. Obs. Pulmon. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Russo, C., Valle, M.S., Casabona, A., Spicuzza, L., Sambataro, G., and Malaguarnera, L. (2022). Vitamin D Impacts on Skeletal Muscle Dysfunction in Patients with COPD Promoting Mitochondrial Health. Biomedicines, 10.","DOI":"10.3390\/biomedicines10040898"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1177\/147323001204000321","article-title":"Evaluation of the significance of circulating insulin-like growth factor-1 and C-reactive protein in patients with chronic obstructive pulmonary disease","volume":"40","author":"Ye","year":"2012","journal-title":"J. Int. Med. Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1530\/EJE-18-0076","article-title":"The relationship between serum IGF-1, handgrip strength, physical performance and falls in elderly men and women","volume":"179","author":"Vlot","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1177\/1479972318757468","article-title":"Elevated circulating ghrelin in patients with COPD: A meta-analysis","volume":"15","author":"Zhang","year":"2018","journal-title":"Chron. Respir. Dis."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1210\/endrev\/bnad012","article-title":"AMPK and the Endocrine Control of Metabolism","volume":"44","author":"Townsend","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1586\/17476348.2016.1157472","article-title":"Changes in structural and metabolic muscle characteristics following exercise-based interventions in patients with COPD: A systematic review","volume":"10","author":"Spruit","year":"2016","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Nyberg, A., Milad, N., Martin, M., Patoine, D., Morissette, M.C., Saey, D., and Maltais, F. (2022). Role of progression of training volume on intramuscular adaptations in patients with chronic obstructive pulmonary disease. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.873465"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1016\/j.chest.2020.12.005","article-title":"Effects of Low-Load\/High-Repetition Resistance Training on Exercise Capacity, Health Status, and Limb Muscle Adaptation in Patients with Severe COPD: A Randomized Controlled Trial","volume":"159","author":"Nyberg","year":"2021","journal-title":"Chest"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1159\/000521241","article-title":"Definition and Diagnostic Criteria for Sarcopenic Obesity: ESPEN and EASO Consensus Statement","volume":"15","author":"Donini","year":"2022","journal-title":"Obes. Facts"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.chest.2022.11.040","article-title":"Differential Impact of Low Fat-Free Mass in People with COPD Based on BMI Classifications: Results from the COPD and Systemic Consequences-Comorbidities Network","volume":"163","author":"Machado","year":"2023","journal-title":"Chest"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4367","DOI":"10.2147\/JIR.S366204","article-title":"Skeletal Myosteatosis is Associated with Systemic Inflammation and a Loss of Muscle Bioenergetics in Stable COPD","volume":"15","author":"Persson","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_113","first-page":"402","article-title":"Detecting sarcopenia in obesity: Emerging new approaches","volume":"27","author":"Zanetti","year":"2024","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1111\/sms.13227","article-title":"Effect of endurance versus resistance training on local muscle and systemic inflammation and oxidative stress in COPD","volume":"28","author":"Thaning","year":"2018","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1111\/sms.13494","article-title":"Effects of concurrent exercise training on muscle dysfunction and systemic oxidative stress in older people with COPD","volume":"29","author":"Alcazar","year":"2019","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1111\/sms.14428","article-title":"Residual effects of 12 weeks of power-oriented resistance training plus high-intensity interval training on muscle dysfunction, systemic oxidative damage, and antioxidant capacity after 10 months of training cessation in older people with COPD","volume":"33","author":"Carretero","year":"2023","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Catteau, M., Passerieux, E., Blervaque, L., Gouzi, F., Ayoub, B., Hayot, M., and Pomi\u00e8s, P. (2021). Response to Electrostimulation Is Impaired in Muscle Cells from Patients with Chronic Obstructive Pulmonary Disease. Cells, 10.","DOI":"10.3390\/cells10113002"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Souza-Santos, D., Taiar, R., Bachur, J.A., Torres-Nunes, L., Monteiro-Oliveira, B.B., de Oliveira Guedes-Aguiar, E., Coelho-Oliveira, A.C., Amaral Mendon\u00e7a, V., Rodrigues Lacerda, A.C., and Sonza, A. (2024). Effects of Physical Exercise on the Body Composition and Functionality in Individuals with Chronic Obstructive Pulmonary Disease: A Systematic Review. Diagnostics, 14.","DOI":"10.3390\/diagnostics14242847"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/220\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T05:18:04Z","timestamp":1769318284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/3\/220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":118,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["cells15030220"],"URL":"https:\/\/doi.org\/10.3390\/cells15030220","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]}}}