Sarcopenic Obesity in Cancer Patients: Focus on Pathogenesis

Wilson Matthew Raffaello, Andree Kurniawan

Abstract


Introduction: Sarcopenic obesity is an emerging problem in cancer patients. However, this is often difficult to diagnose without the measurement of body composition. Sarcopenic obesity is associated with increased mortality, chemo-toxicity, and other complications in cancer patients. Until now, there is scarce information about sarcopenic obesity in the cancer population.

Method: We identified 1955 articles related to sarcopenic obesity in adult cancer patients using PubMed, PubMed Central, and Cochrane Library databases from January 1, 1989, until January 1, 2020. Firstly, we screened the titles and abstracts which mentioned sarcopenic and obesity, especially in pathogenesis. 29 articles could proceed to the next step; then, they were screened for the full text. All steps were reviewed by two authors.

Results: At last, they were 9 articles included. Sarcopenic obesity is defined as the coexistence of sarcopenia and obesity, an increase in fat mass in the body. Sarcopenic obesity carried cumulative risks from each of the two individual body compositions. CT-scan offers the highest available precision in determining body composition parameters, especially in the cancer population. Multiple causes and interactions between hormonal changes, aging, disuse, neuronal, poor nutrition, physical inactivity, and low-grade inflammation played roles. Sarcopenic obesity is associated with chemotherapy toxicity. High protein intake should be initiated to ensure adequate protein intake. Resistance training is beneficial in improving muscle mass and strength by focusing on strength training, flexibility, and balance.

Conclusions: Sarcopenic obesity is an emerging problem but is often neglected. Further research needs to be conducted especially in explaining the pathogenesis of sarcopenic obesity. The combination of physical exercise and diet modification is the best management to improve sarcopenia obesity in cancer patients.


Keywords


cancer, sarcopenic, obesity, low muscle mass

References


Kalinkovich A, Livshits G. Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis. Ageing Res Rev. 2017;35:200-21.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16-31.

Santilli V, Bernetti A, Mangone M, Paoloni M. Clinical definition of sarcopenia. Clin Cases Miner Bone Metab. 2014;11(3):177-80.

Polyzos SA, Margioris AN. Sarcopenic obesity. Hormones. 2018;17(3):321–31.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.

Deluche E, Leobon S, Desport JC, Venat-Bouvet L, Usseglio J, Tubiana-Mathieu N. Impact of body composition on outcome in patients with early breast cancer. Support Care Cancer. 2018;26(3):861–8.

Gruber ES, Jomrich G, Tamandl D, Gnant M, Schindl M, Sahora K. Sarcopenia and sarcopenic obesity are independent adverse prognostic factors in resectable pancreatic ductal adenocarcinoma. PLoS One. 2019;14(5):e0215915.

Lodewick TM, van Nijnatten TJA, van Dam RM, van Mierlo K, Dello SAWG, Neumann UP, et al. Are sarcopenia, obesity and sarcopenic obesity predictive of outcome in patients with colorectal liver metastases? HPB. 2015;17(5):438–46.

Antoun S, Borget I, Lanoy E. Impact of sarcopenia on the prognosis and treatment toxicities in patients diagnosed with cancer. Curr Opin Support Palliat Care. 2013;7(4):383–9.

Anandavadivelan P, Brismar TB, Nilsson M, Johar AM, Martin L. Sarcopenic obesity: A probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients. Clin Nutr. 2016;35(3):724–30.

Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35.

Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz A V., et al. The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study. Journals

Gerontol Ser A Biol Sci Med Sci. 2006;61(10):1059–64.

Hughes VA, Roubenoff R, Wood M, Frontera WR, Evans WJ, Fiatarone Singh MA. Anthropometric assessment of 10-y changes in body composition in the elderly. Am J Clin Nutr. 2004;80(2):475–82.

Song M-Y, Ruts E, Kim J, Janumala I, Heymsfield S, Gallagher D. Sarcopenia and increased adipose tissue infiltration of muscle in elderly African American women. Am J Clin Nutr. 2004;79(5):874–80.

Batsis JA, Villareal DT. Sarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies. Nat Rev Endocrinol. 2018;14(9):513–37.

Meza-Junco J, Montano-Loza AJ, Baracos VE, Prado CMM, Bain VG, Beaumont C, et al. Sarcopenia as a prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol. 2013;47(10):861–70.

Baracos VE, Arribas L. Sarcopenic obesity: Hidden muscle wasting and its impact for survival and complications of cancer therapy. Ann Oncol. 2018;29(Supplement 2):ii1–9.

Villareal DT, Apovian CM, Kushner RF, Klein S, American Society for Nutrition, NAASO, The Obesity Society. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am J Clin Nutr. 2005;82(5):923–34.

Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. American association of clinical endocrinologists and American college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22:1–203.

Prado CMM, Wells JCK, Smith SR, Stephan BCM, Siervo M. Sarcopenic obesity: A Critical appraisal of the current evidence. Clin Nutr. 2012;31(5):583–601.

Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, et al. Epidemiology of Sarcopenia among the Elderly in New Mexico. Am J Epidemiol. 1998;147(8):755–63.

Janssen I, Heymsfield SB, Ross R. Low Relative Skeletal Muscle Mass (Sarcopenia) in Older Persons Is Associated with Functional Impairment and Physical Disability. J Am Geriatr Soc. 2002;50(5):889–96.

Metter EJ, Talbot LA, Schrager M, Conwit R. Skeletal muscle strength as a predictor of all-cause mortality in healthy men. J Gerontol A Biol Sci Med Sci. 2002;57(10):B359-65.

Cosquéric G, Sebag A, Ducolombier C, Thomas C, Piette F, Weill-Engerer S. Sarcopenia is predictive of nosocomial infection in care of the elderly. Br J Nutr. 2006;96(5):895–901.

Pichard C, Kyle UG, Morabia A, Perrier A, Vermeulen B, Unger P. Nutritional assessment: lean body mass depletion at hospital admission is associated with an increased length of stay. Am J Clin Nutr. 2004;79(4):613–8.

Del Fabbro E, Parsons H, Warneke CL, Pulivarthi K, Litton JK, Dev R, et al. The relationship between body composition and response to neoadjuvant chemotherapy in women with operable breast cancer. Oncologist. 2012;17(10):1240–5.

Dalal S, Hui D, Bidaut L, Lem K, Del Fabbro E, Crane C, et al. Relationships Among Body Mass Index, Longitudinal Body Composition Alterations, and Survival in Patients With Locally Advanced Pancreatic Cancer Receiving Chemoradiation: A Pilot Study. J Pain Symptom Manage. 2012;44(2):181–91.

Malietzis G, Currie AC, Athanasiou T, Johns N, Anyamene N, Glynne-Jones R, et al. Influence of body composition profile on outcomes following colorectal cancer surgery. Br J Surg. 2016;103(5):572–80.

Rier HN, Jager A, Sleijfer S, van Rosmalen J, Kock MCJM, Levin M-D. Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy. The Breast. 2017;31:9–15.

Grotenhuis BA, Shapiro J, van Adrichem S, de Vries M, Koek M, Wijnhoven BPL, et al. Sarcopenia/Muscle Mass is not a Prognostic Factor for Short- and Long-Term Outcome After Esophagectomy for Cancer. World J Surg. 2016;40(11):2698–704.

Mourtzakis M, Prado CMM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.

Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019;48(1):16–31.

Xu W, Perera S, Medich D, Fiorito G, Wagner J, Berger LK, et al. Height loss, vertebral fractures, and the misclassification of osteoporosis. Bone. 2011;48(2):307–11.

Sayer AA, Syddall H, Martin H, Patel H, Baylis D, Cooper C. The developmental origins of sarcopenia. J Nutr Health Aging. 2008;12(7):427–32.

Conley KE, Esselman PC, Jubrias SA, Cress ME, Inglin B, Mogadam C, et al. Ageing, muscle properties and maximal O(2) uptake rate in humans. J Physiol. 2000;526 Pt 1(Pt 1):211–7.

Yancik R. Population Aging and Cancer. Cancer J. 2005;11(6):437–41.

Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, et al. Muscle Mass, Muscle Strength, and Muscle Fat Infiltration as Predictors of Incident Mobility Limitations in Well-Functioning Older Persons. Journals Gerontol Ser A Biol Sci Med Sci. 2005;60(3):324–33.

Schrauwen-Hinderling VB, Hesselink MKC, Schrauwen P, Kooi ME. Intramyocellular Lipid Content in Human Skeletal Muscle. Obesity. 2006;14(3):357–67.

Berg MMGA van den, Kok DE, Posthuma L, Kamps L, Kelfkens CS, Buist N, et al. Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I–IIIB breast cancer receiving chemotherapy. Breast Cancer Res Treat. 2019;173(2):475.

Enns DL, Tiidus PM. Estrogen influences satellite cell activation and proliferation following downhill running in rats. J Appl Physiol. 2008;104(2):347–53.

Gambacciani M, Ciaponi M, Cappagli B, De Simone L, Orlandi R, Genazzani AR. Prospective evaluation of body weight and body fat distribution in early postmenopausal women with and without hormonal replacement therapy. Maturitas. 2001;39(2):125–32.

Kadi F. Cellular and molecular mechanisms responsible for the action of testosterone on human skeletal muscle. A basis for illegal performance enhancement. Br J Pharmacol. 2008;154(3):522–8.

Bondanelli M, Ambrosio MR, Margutti A, Franceschetti P, Zatelli MC, degli Uberti EC. Activation of the Somatotropic Axis by Testosterone in Adult Men: Evidence for a Role of Hypothalamic Growth Hormone-Releasing Hormone. Neuroendocrinology. 2003 Jun;77(6):380–7.

Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol Metab. 1995;269(5):E820–6.

LeBlanc ES, Wang PY, Lee CG, Barrett-Connor E, Cauley JA, Hoffman AR, et al. Higher Testosterone Levels Are Associated with Less Loss of Lean Body Mass in Older Men. J Clin Endocrinol Metab. 2011;96(12):3855–63.

Miller KK. Androgen deficiency: effects on body composition. Pituitary. 2009;12(2):116–24.

Schrager MA, Metter EJ, Simonsick E, Ble A, Bandinelli S, Lauretani F, et al. Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol. 2007;102(3):919–25.

Forsythe LK, Wallace JMW, Livingstone MBE. Obesity and inflammation: the effects of weight loss. Nutr Res Rev. 2008;21(2):117–33.

Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract. 2005;69(1):29–35.

Zamboni M, Mazzali G, Fantin F, Rossi A, Di Francesco V. Sarcopenic obesity: A new category of obesity in the elderly. Nutr Metab Cardiovasc Dis. 2008;18(5):388–95.

Yeap BB, Paul Chubb SA, Lopez D, Ho KKY, Hankey GJ, Flicker L. Associations of insulin-like growth factor-I and its binding proteins and testosterone with frailty in older men. Clin Endocrinol (Oxf). 2013;78(5):752–9.

Hamrick MW. Role of the Cytokine-like Hormone Leptin in Muscle-bone Crosstalk with Aging. J bone Metab. 2017;24(1):1–8.

Wang Y, Wang X, Lau WB, Yuan Y, Booth D, Li J-J, et al. Adiponectin Inhibits Tumor Necrosis Factor-α–Induced Vascular Inflammatory Response via Caveolin-Mediated Ceramidase Recruitment and Activation. Circ Res. 2014;114(5):792–805.

Shulman GI. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014;371(12):1131–41.

Cartwright M, Tchkonia T, Kirkland J. Aging in adipocytes: Potential impact of inherent, depot-specific mechanisms. Exp Gerontol. 2007;42(6):463–71.

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.

Feliciano EMC, Kroenke CH, Meyerhardt JA, Prado CM, Bradshaw PT, Kwan ML, et al. Association of Systemic Inflammation and Sarcopenia With Survival in Nonmetastatic Colorectal Cancer: Results From the C SCANS Study. JAMA Oncol. 2017;3(12):e172319.

Stenholm S, Harris TB, Rantanen T, Visser M, Kritchevsky SB, Ferrucci L. Sarcopenic obesity: definition, cause and consequences. Curr Opin Clin Nutr Metab Care. 2008;11(6):693–700.

Kob R, Bollheimer LC, Bertsch T, Fellner C, Djukic M, Sieber CC, et al. Sarcopenic obesity: molecular clues to a better understanding of its pathogenesis? Biogerontology. 2015;16(1):15–29.

Stinkens R, Goossens GH, Jocken JWE, Blaak EE. Targeting fatty acid metabolism to improve glucose metabolism. Obes Rev. 2015;16(9):715–57.

Aon MA, Bhatt N, Cortassa SC. Mitochondrial and cellular mechanisms for managing lipid excess. Front Physiol. 2014;5:282.

Bruce CR, Anderson MJ, Carey AL, Newman DG, Bonen A, Kriketos AD, et al. Muscle Oxidative Capacity Is a Better Predictor of Insulin Sensitivity than Lipid Status. J Clin Endocrinol Metab. 2003;88(11):5444–51.

Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB. Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr. 2007;85(2):377–84.

Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis. 2009;14(12):1484–95.

Nilsson MI, Dobson JP, Greene NP, Wiggs MP, Shimkus KL, Wudeck E V., et al. Abnormal protein turnover and anabolic resistance to exercise in sarcopenic obesity. FASEB J. 2013;27(10):3905–16.

Carnio S, LoVerso F, Baraibar MA, Longa E, Khan MM, Maffei M, et al. Autophagy Impairment in Muscle Induces Neuromuscular Junction Degeneration and Precocious Aging. Cell Rep. 2014;8(5):1509–21.

Marcell TJ. Sarcopenia: causes, consequences, and preventions. J Gerontol A Biol Sci Med Sci. 2003;58(10):M911-6.

Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise. Exp Gerontol. 2010;45(2):138–48.

Shefer G, Rauner G, Stuelsatz P, Benayahu D, Yablonka-Reuveni Z. Moderate-intensity treadmill running promotes expansion of the satellite cell pool in young and old mice. FEBS J. 2013;280(17):4063–73.

Zwetsloot KA, Childs TE, Gilpin LT, Booth FW. Non-passaged muscle precursor cells from 32-month old rat skeletal muscle have delayed proliferation and differentiation. Cell Prolif. 2013;46(1):45–57.

Åkerberg D, Ansari D, Andersson R. Re-evaluation of classical prognostic factors in resectable ductal adenocarcinoma of the pancreas. World J Gastroenterol. 2016;22(28):6424.

Heidelberger V, Goldwasser F, Kramkimel N, Jouinot A, Huillard O, Boudou-Rouquette P, et al. Sarcopenic overweight is associated with early acute limiting toxicity of anti-PD1 checkpoint inhibitors in melanoma patients. Invest New Drugs. 2017;35(4):436–41.

Joglekar S, Nau PN, Mezhir JJ. The impact of sarcopenia on survival and complications in surgical oncology: A review of the current literature. J Surg Oncol. 2015;112(5):503–9.

Levolger S, van Vugt JLA, de Bruin RWF, IJzermans JNM. Systematic review of sarcopenia in patients operated on for gastrointestinal and hepatopancreatobiliary malignancies. Br J Surg. 2015;102(12):1448–58.

Davis MP, Panikkar R. Sarcopenia associated with chemotherapy and targeted agents for cancer therapy. Ann Palliat Med. 2019;8(1):86–101.

Okumura S, Kaido T, Hamaguchi Y, Kobayashi A, Shirai H, Yao S, et al. Visceral Adiposity and Sarcopenic Visceral Obesity are Associated with Poor Prognosis After Resection of Pancreatic Cancer. Ann Surg Oncol. 2017;24(12):3732–40.

Daly LE, Ní Bhuachalla ÉB, Power DG, Cushen SJ, James K, Ryan AM. Loss of skeletal muscle during systemic chemotherapy is prognostic of poor survival in patients with foregut cancer. J Cachexia Sarcopenia Muscle. 2018;9(2):315–25.

Carneiro IP, Mazurak VC, Prado CM. Clinical Implications of Sarcopenic Obesity in Cancer. Curr Oncol Rep. 2016;18(10):62.

Pecorelli N, Carrara G, De Cobelli F, Cristel G, Damascelli A, Balzano G, et al. Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery. Br J Surg. 2016;103(4):434–42.

Tan BHL, Birdsell LA, Martin L, Baracos VE, Fearon KCH. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009;15(22):6973–9.

Rollins KE, Tewari N, Ackner A, Awwad A, Madhusudan S, Macdonald IA, et al. The impact of sarcopenia and myosteatosis on outcomes of unresectable pancreatic cancer or distal

cholangiocarcinoma. Clin Nutr. 2016;35(5):1103–9.

Palmela C, Velho S, Agostinho L, Branco F, Santos M, Santos MPC, et al. Body composition as a prognostic factor of neoadjuvant chemotherapy toxicity and outcome in patients with locally advanced gastric cancer. J Gastric Cancer. 2017;17(1):74–87.

Cushen SJ, Power DG, Murphy KP, McDermott R, Griffin BT, Lim M, et al. Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel. Clin Nutr ESPEN. 2016;13:e39–45.

Malietzis G, Johns N, Al-Hassi HO, Knight SC, Kennedy RH, Fearon KCH, et al. Low Muscularity and Myosteatosis Is Related to the Host Systemic Inflammatory Response in Patients Undergoing Surgery for Colorectal Cancer. Ann Surg. 2016;263(2):320–5.

Sandini M, Bernasconi DP, Fior D, Molinelli M, Ippolito D, Nespoli L, et al. A high visceral adipose tissue-to-skeletal muscle ratio as a determinant of major complications after pancreatoduodenectomy for cancer. Nutrition. 2016;32(11–12):1231–7.

Nishigori T, Tsunoda S, Okabe H, Tanaka E, Hisamori S, Hosogi H, et al. Impact of Sarcopenic Obesity on Surgical Site Infection after Laparoscopic Total Gastrectomy. Ann Surg Oncol. 2016;23(S4):524–31.

Srikanthan P, Hevener AL, Karlamangla AS. Sarcopenia Exacerbates Obesity-Associated Insulin Resistance and Dysglycemia: Findings from the National Health and Nutrition Examination Survey III. Earnest CP, editor. PLoS One. 2010;5(5):e10805.

Pierpont YN, Dinh TP, Salas RE, Johnson EL, Wright TG, Robson MC, et al. Obesity and Surgical Wound Healing: A Current Review. ISRN Obes. 2014;2014:1–13.

Stanisavljevic NS, Marisavljevic DZ. Weight and body composition changes during R-CHOP chemotherapy in patients with non-Hodgkin’s lymphoma and their impact on dose intensity and toxicity. J BUON. 15(2):290–6.

Nattenmüller J, Wochner R, Muley T, Steins M, Hummler S, Teucher B, et al. Prognostic Impact of CT-Quantified Muscle and Fat Distribution before and after First-Line-Chemotherapy in Lung Cancer Patients. Singh PK, editor. PLoS One. 2017;12(1):e0169136.

Kurniawan A. Sarcopenia in Cancer Patients. Indones J Cancer. 2019;13(3):96.

Montero-Fernández N, Serra-Rexach JA. Role of exercise on sarcopenia in the elderly. Eur J Phys Rehabil Med. 2013;49(1):131–43.

Villanueva MG, Lane CJ, Schroeder ET. Short rest interval lengths between sets optimally enhance body composition and performance with 8 weeks of strength resistance training in older men. Eur J Appl Physiol. 2015;115(2):295–308.

Villareal DT, Miller B V, Banks M, Fontana L, Sinacore DR, Klein S. Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr. 2006;84(6):1317–23.


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