Pathogenetic aspects of cachexia
https://doi.org/10.14341/omet10173
Abstract
The relevance of cachexia syndrome is determined by its high prevalence in clinical practice. It accompanies the course of not only oncological diseases, but also the majority of chronic somatic pathologies, such as chronic heart failure, renal failure, diabetes mellitus, chronic obstructive pulmonary disease, acquired immunodeficiency syndrome, rheumatoid arthritis, Alzheimer’s disease and others. It is known that even a slight weight loss in patients can determine an unfavorable prognosis of the underlying disease and reduce the effectiveness of therapy, and sometimes it becomes the direct cause of death of the patient.
Cachexia is a complex metabolic syndrome, which is based on a violation of the central regulation of metabolism. The dangerous combination of decreased appetite (anorexia) and increased metabolism is the result of an imbalance in energy exchange. Treatment of cachexia syndrome is ineffective and limited in means. Given the progressive and irreversible nature of this syndrome, early diagnosis and prevention of its development are the primary task of the doctor.
The article describes the main pathogenetic aspects of the development of cachexia syndrome. They can be common in different diseases. The article discusses the difficulties of diagnosing cachexia syndrome, the possibilities and prospects of treatment.
About the Authors
Irina S. Klochkova
N.N. Burdenko national medical research center of neurosurgery
Russian Federation
Russian Federation
MD
Ludmila I. Astafyeva
N.N. Burdenko national medical research center of neurosurgery
Russian Federation
Russian Federation
MD, PhD
Boris A. Kadashev
N.N. Burdenko national medical research center of neurosurgery
Russian Federation
Russian Federation
MD, PhD, Professor
Yuliya G. Sidneva
N.N. Burdenko national medical research center of neurosurgery
Russian Federation
Russian Federation
MD, PhD
Pavel L. Kalinin
N.N. Burdenko national medical research center of neurosurgery
Russian Federation
Russian Federation
MD, PhD
References
1. Katz AM, Katz PB. Diseases of the heart in the works of Hippocrates. Br Heart J. 1962;24:257-264. DOI:10.1136/hrt.24.3.257
2. Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793-799. DOI:10.1016/j.clnu.2008.06.013
3. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489-495. DOI:10.1016/s1470-2045(10)70218-7
4. Morley JE, Thomas DR, Wilson M-MG. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83(4):735-743. DOI:10.1093/ajcn/83.4.735
5. Tan BHL, Fearon KCH. Cachexia: prevalence and impact in medicine. Curr Opin Clin Nutr Metab Care. 2008;11(4):400-407. DOI:10.1097/MCO.0b013e328300ecc1
6. Jager-Wittenaar H, Dijkstra PU, Dijkstra G, et al. High prevalence of cachexia in newly diagnosed head and neck cancer patients: An exploratory study. Nutrition. 2017;35:114-118. DOI:10.1016/j.nut.2016.11.008
7. Martin L, Senesse P, Gioulbasanis I, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015;33(1):90-99. DOI:10.1200/JCO.2014.56.1894
8. Norman K, Pichard C, Lochs H, Pirlich M. Prognostic impact of disease-related malnutrition. Clin Nutr. 2008;27(1):5-15. DOI:10.1016/j.clnu.2007.10.007
9. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle. 2010;1(1):1-5. DOI:10.1007/s13539-010-0002-6
10. Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9:e9.
11. Caccialanza R, Cereda E, Pinto C, et al. Awareness and consideration of malnutrition among oncologists: Insights from an exploratory survey. Nutrition. 2016;32(9):1028-1032. DOI:10.1016/j.nut.2016.02.005
12. Rauh S, Antonuzzo A, Bossi P, et al. Nutrition in patients with cancer: a new area for medical oncologists? A practising oncologist’s interdisciplinary position paper. ESMO Open. 2018;3(4):e000345. DOI:10.1136/esmoopen-2018-000345
13. Waitzberg DL, Caiaffa WT, Correia MITD. Hospital malnutrition: the Brazilian national survey (IBRANUTRI): a study of 4000 patients. Nutrition. 2001;17(7-8):573-580. DOI:10.1016/s0899-9007(01)00573-1
14. Руководство по клиническому питанию. / Под ред. Луфта В.М., Багненко С.Ф., Щербука Ю.А. — СПб.: АРТ-ЭКСПРЕСС; 2010. [Luft VM, Bagnenko SF, Shcherbuk YA, editors. Rukovodstvo po klinicheskomu pitaniyu. Saint Petersburg: ART-EKSPRESS; 2010. (In Russ).]
15. Хорошилов И.Е. Руководство по парентеральному и энтеральному питанию. — СПб.: Нордмед-издат; 2000. [Khoroshilov IE. Rukovodstvo po parenteral’nomu i enteral’nomu pitaniyu. Saint Petersburg: Nordmed-izdat; 2000. (In Russ).]
16. Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol. 2013;10(2):90-99. DOI:10.1038/nrclinonc.2012.209
17. Anderson LJ, Albrecht ED, Garcia JM. Update on Management of Cancer-Related Cachexia. Curr Oncol Rep. 2017;19(1):3. DOI:10.1007/s11912-017-0562-0
18. bionco.ru [интернет]. Индекс Карновского/Шкала EGOC-ВОЗ [доступ от 17.03.2020]. Доступ по ссылке: http://www.bionco.ru/tables/carnovskyindex_scaleecog/. [Bionco.ru [Internet]. Karnovskiy Index/EGOC-WHO Scale [cited 2010 Mar 17]. Available from: http://www.bionco.ru/tables/carnovskyindex_scaleecog/. (In Russ).]
19. Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. The Anatomical Record. 1940;78(2):149-172. DOI:10.1002/ar.1090780203
20. Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661-671. DOI:10.1038/35007534
21. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571-578. DOI:10.1038/nn1455
22. Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol. 2005;184(2):291-318. DOI:10.1677/joe.1.05866
23. Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009;2009:141753. DOI:10.1155/2009/141753
24. Kalra SP, Dube MG, Pu S, et al. Interacting appetite-regulating pathays in the hypothalamic regulation of body weight. Endocr Rev. 1999;20(1):68-100. DOI:10.1210/edrv.20.1.0357
25. Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72-76. DOI:10.1038/29993
26. Upadhya MA, Nakhate KT, Kokare DM, et al. CART peptide in the nucleus accumbens shell acts downstream to dopamine and mediates the reward and reinforcement actions of morphine. Neuropharmacology. 2012;62(4):1823-1833. DOI:10.1016/j.neuropharm.2011.12.004
27. Elmquist JK. Hypothalamic pathways underlying the endocrine, autonomic, and behavioral effects of leptin. Int J Obes Relat Metab Disord. 2001;25 Suppl 5:S78-82. DOI:10.1038/sj.ijo.0801918
28. Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr Rev. 2010;31(4):506-543. DOI:10.1210/er.2009-0037
29. Cummings DE, Schwartz MW. Melanocortins and body weight: a tale of two receptors. Nat Genet. 2000;26(1):8-9. DOI:10.1038/79223
30. Herzog H. Neuropeptide Y and energy homeostasis: insights from Y receptor knockout models. Eur J Pharmacol. 2003;480(1-3):21-29. DOI:10.1016/j.ejphar.2003.08.089
31. Billington CJ, Briggs JE, Grace M, Levine AS. Effects of intracerebroventricular injection of neuropeptide Y on energy metabolism. Am J Physiol. 1991;260(2 Pt 2):R321-327. DOI:10.1152/ajpregu.1991.260.2.R321
32. Ollmann MM, Wilson BD, Yang YK, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278(5335):135-138. DOI:10.1126/science.278.5335.135
33. Neary NM, Goldstone AP, Bloom SR. Appetite regulation: from the gut to the hypothalamus. Clin Endocrinol. 2004;60(2):153-160. DOI:10.1046/j.1365-2265.2003.01839.x
34. Van Gaal LF, Wauters MA, Mertens IL, et al. Clinical endocrinology of human leptin. Int J Obes Relat Metab Disord. 1999;23 Suppl 1:29-36. DOI:10.1038/sj.ijo.0800792
35. Романцова Т.И., Волкова Г. Е. Лептин и грелин: антагонизм и взаимодействие в регуляции энергетического обмена. // Ожирение и метаболизм. — 2005. — Т. 2. — №2. — С. 2-9. [Romantsova TI, Volkova GE. Leptin i grelin: antagonizm i vzaimodeystvie v regulyatsii energeticheskogo obmena. Obesity and metabolism. 2005;2(2):2-9. (In Russ).] DOI:10.14341/2071-8713-4924
36. Cinti S, Frederich RC, Zingaretti MC, et al. Immunohistochemical Localization of Leptin and Uncoupling Protein in White and Brown Adipose Tissue1. Endocrinology. 1997;138(2):797-804. DOI:10.1210/endo.138.2.4908
37. Joost HG. Appetite Control. Berlin, Heidelberg: Springer; 2012. DOI:10.1007/978-3-642-24716-3
38. Friedman JM. Leptin, leptin receptors, and the control of body weight. Nutr Rev. 1998;56(2 Pt 2):s38-46; discussion s54-75. DOI:10.1111/j.1753-4887.1998.tb01685.x
39. Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature. 1995;377(6549):527-529. DOI:10.1038/377527a0
40. van der Lely AJ, Tschop M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev. 2004;25(3):426-457. DOI:10.1210/er.2002-0029
41. Tschop M, Weyer C, Tataranni PA, et al. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50(4):707-709. DOI:10.2337/diabetes.50.4.707
42. Tolle V, Kadem M, Bluet-Pajot MT, et al. Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women. J Clin Endocrinol Metab. 2003;88(1):109-116. DOI:10.1210/jc.2002-020645
43. Nagaya N, Uematsu M, Kojima M, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation. 2001;104(17):2034-2038. DOI:10.1161/hc4201.097836
44. Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003;9(2):774-778.
45. Deboer MD, Zhu X, Levasseur PR, et al. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology. 2008;149(2):827-835. DOI:10.1210/en.2007-1046
46. DeBoer MD, Zhu XX, Levasseur P, et al. Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology. 2007;148(6):3004-3012. DOI:10.1210/en.2007-0016
47. Garcia JM, Boccia RV, Graham CD, et al. Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials. Lancet Oncol. 2015;16(1):108-116. DOI:10.1016/s1470-2045(14)71154-4
48. Романцова Т.И. Основные принципы регуляции энергетического баланса. // Consilium medicum. — 2014. — Т. 16. — №4. — С. 75-79. [Romantsova TI. Osnovnye printsipy regulyatsii energeticheskogo balansa. Consilium medicum. 2014;16(4):75-79. (In Russ).]
49. Hussain SS, Bloom SR. The regulation of food intake by the gut-brain axis: implications for obesity. Int J Obes (Lond). 2013;37(5):625-633. DOI:10.1038/ijo.2012.93
50. Grossberg AJ, Scarlett JM, Marks DL. Hypothalamic mechanisms in cachexia. Physiol Behav. 2010;100(5):478-489. DOI:10.1016/j.physbeh.2010.03.011
51. Petruzzelli M, Wagner EF. Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev. 2016;30(5):489-501. DOI:10.1101/gad.276733.115
52. Anker SD, Ponikowski PP, Clark AL, et al. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J. 1999;20(9):683-693. DOI:10.1053/euhj.1998.1446
53. Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care. 2005;8(3):265-269. DOI:10.1097/01.mco.0000165004.93707.88
54. Sonti G, Ilyin SE, Plata-Salaman CR. Anorexia induced by cytokine interactions at pathophysiological concentrations. Am J Physiol. 1996;270(6 Pt 2):R1394-1402. DOI:10.1152/ajpregu.1996.270.6.R1394
55. Plata-Salaman CR. Anorexia induced by activators of the signal transducer gp 130. Neuroreport. 1996;7(3):841-844. DOI:10.1097/00001756-199602290-00038
56. Petruzzelli M, Schweiger M, Schreiber R, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 2014;20(3):433-447. DOI:10.1016/j.cmet.2014.06.011
57. Larson CJ. Translational Pharmacology and Physiology of Brown Adipose Tissue in Human Disease and Treatment. Handb Exp Pharmacol. 2019;251:381-424. DOI:10.1007/164_2018_184
58. Wolsk E, Mygind H, Grondahl TS, et al. IL-6 selectively stimulates fat metabolism in human skeletal muscle. Am J Physiol Endocrinol Metab. 2010;299(5):E832-840. DOI:10.1152/ajpendo.00328.2010
59. Ibebunjo C, Chick JM, Kendall T, et al. Genomic and proteomic profiling reveals reduced mitochondrial function and disruption of the neuromuscular junction driving rat sarcopenia. Mol Cell Biol. 2013;33(2):194-212. DOI:10.1128/MCB.01036-12
60. Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16(2):153-166. DOI:10.1016/j.cmet.2012.06.011
61. Penna F, Minero VG, Costamagna D, et al. Anti-cytokine strategies for the treatment of cancer-related anorexia and cachexia. Expert Opin Biol Ther. 2010;10(8):1241-1250. DOI:10.1517/14712598.2010.503773
62. Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol. 2013;10(2):90-99. DOI:10.1038/nrclinonc.2012.209
63. Weimann A, Braga M, Carli F, et al. ESPEN guideline: Clinical nutrition in surgery. Clin Nutr. 2017;36(3):623-650. DOI:10.1016/j.clnu.2017.02.013
64. Хорошилов И.Е. Персонифицированный подход к нутриционной поддержке пациентов с недостаточным и избыточным питанием. // Фарматека. — 2018. — №2. — С. 48-52. [Khoroshilov IE. Personified approach to nutritional support of patients with undernutrition and overnutrition. Farmateka. 2018;(2):48-52. (In Russ).] DOI:10.18565/pharmateca.2018.2.48-52
65. Снеговой А.В., Бесова Н.С., Веселов А.В., и др. Практические рекомендации по нутритивной поддержке у онкологических больных. // Злокачественные опухоли. — 2016. — №4S2. — С. 434-450. [Snegovoy AV, Besova NS, Veselov AV, et al. Prakticheskie rekomendatsii po nutritivnoy podderzhke u onkologicheskikh bol’nykh. Zlokachestvennye opukholi. 2016;(4S2):434-450. (In Russ).] DOI:10.18027/2224-5057-2016-4s2-434-450
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Klochkova I.S., Astafyeva L.I., Kadashev B.A., Sidneva Yu.G., Kalinin P.L. Pathogenetic aspects of cachexia. Obesity and metabolism. 2020;17(1):33-40. (In Russ.) https://doi.org/10.14341/omet10173
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