ometendoОжирение и метаболизмObesity and metabolism2071-87132306-5524Endocrinology Research Centre10.14341/omet10173ometendo-10173Research ArticleОбзор литературыReviewПатогенетические аспекты синдрома кахексииPathogenetic aspects of cachexiahttps://orcid.org/0000-0002-7440-4687КлочковаИрина СергеевнаKlochkovaIrina S.

врач клинико-диагностическое отделение

MD

IKlochkova@nsi.ruhttps://orcid.org/0000-0003-4480-1902АстафьеваЛюдмила ИгоревнаAstafyevaLudmila I.

д.м.н.

MD, PhD

last@nsi.ruhttps://orcid.org/0000-0001-8344-3381КадашевБорис АлександровичKadashevBoris A.

д.м.н., профессор

MD, PhD, Professor

kadashev@nsi.ruhttps://orcid.org/0000-0003-2733-5874СидневаЮлия ГеннадьевнаSidnevaYuliya G.

к.м.н.

MD, PhD

ysidneva@nsi.ruhttps://orcid.org/0000-0001-9333-9473КалининПавел ЛьвовичKalininPavel L.

д.м.н.

MD, PhD

pkalinin@nsi.ruНaциональный медицинский исследовательский центр нейрохирургии имени академика Н.Н. БурденкоРоссияN.N. Burdenko national medical research center of neurosurgeryRussian Federation2020010620201713340Copyright © Клочкова И.С., Астафьева Л.И., Кадашев Б.А., Сиднева Ю.Г., Калинин П.Л., 20202020Клочкова И.С., Астафьева Л.И., Кадашев Б.А., Сиднева Ю.Г., Калинин П.Л.Klochkova I.S., Astafyeva L.I., Kadashev B.A., Sidneva Y.G., Kalinin P.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.omet-endojournals.ru/jour/article/view/10173

Актуальность синдрома кахексии определяется его высокой распространенностью в клинической практике. Он сопровождает течение не только онкологических заболеваний, но и большинства хронических соматических патологий, таких как хроническая сердечная недостаточность, хроническая болезнь почек, сахарный диабет, хроническая обструктивная болезнь легких, синдром приобретенного иммунодефицита, ревматоидный артрит, болезнь Альцгеймера и другие. Известно, что непреднамеренное снижение массы тела определяет неблагоприятный прогноз основного заболевания и снижает эффективность проводимой терапии, а в ряде случаев становится непосредственной причиной смерти пациента.

В настоящее время мы говорим о кахексии как о сложном метаболическом синдроме, в основе которого лежит нарушение центральной регуляции энергетического обмена. Результатом дисбаланса энергообмена становится опасное сочетание сниженного аппетита (анорексии) и усиленного метаболизма. Терапия синдрома кахексии малоэффективна и ограничена небольшим количеством опций. Учитывая прогрессирующий и необратимый характер данного синдрома, своевременная диагностика и профилактика его развития становятся первостепенными задачами врача.

В данной статье мы рассмотрим основные патогенетические аспекты развития синдрома кахексии, общие для разных заболеваний. Обсудим трудности его диагностики, а также возможности и перспективы терапевтического воздействия.

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.

кахексияснижение массы телаанорексияэнергообменпатогенез синдрома кахексииcachexiaweight lossanorexiaenergy exchangepathogenesis of cachexia syndromeReferencesKatz AM, Katz PB. Diseases of the heart in the works of Hippocrates. Br Heart J. 1962;24:257-264. DOI:10.1136/hrt.24.3.257Katz AM, Katz PB. Diseases of the heart in the works of Hippocrates. Br Heart J. 1962;24:257-264. DOI:10.1136/hrt.24.3.257Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793-799. DOI:10.1016/j.clnu.2008.06.013Evans WJ, Morley JE, Argiles J, et al. Cachexia: a new definition. Clin Nutr. 2008;27(6):793-799. DOI:10.1016/j.clnu.2008.06.013Fearon 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)70218-7Fearon 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)70218-7Morley JE, Thomas DR, Wilson M-MG. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83(4):735-743. DOI:10.1093/ajcn/83.4.735Morley JE, Thomas DR, Wilson M-MG. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83(4):735-743. DOI:10.1093/ajcn/83.4.735Tan BHL, Fearon KCH. Cachexia: prevalence and impact in medicine. Curr Opin Clin Nutr Metab Care. 2008;11(4):400-407. DOI:10.1097/MCO.0b013e328300ecc1Tan BHL, Fearon KCH. Cachexia: prevalence and impact in medicine. Curr Opin Clin Nutr Metab Care. 2008;11(4):400-407. DOI:10.1097/MCO.0b013e328300ecc1Jager-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.2016.11.008Jager-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.2016.11.008Martin 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.2014.56.1894Martin 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.2014.56.1894Norman 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.2007.10.007Norman 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.2007.10.007von 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/s13539-010-0002-6von 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/s13539-010-0002-6Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9:e9.Demling RH. Nutrition, anabolism, and the wound healing process: an overview. Eplasty. 2009;9:e9.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.2016.02.005Caccialanza 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.2016.02.005Rauh 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-2018-000345Rauh 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-2018-000345Waitzberg 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)00573-1Waitzberg 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)00573-1Руководство 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).]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).]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).]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).]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.2012.209Fearon 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.2012.209Anderson LJ, Albrecht ED, Garcia JM. Update on Management of Cancer-Related Cachexia. Curr Oncol Rep. 2017;19(1):3. DOI:10.1007/s11912-017-0562-0Anderson LJ, Albrecht ED, Garcia JM. Update on Management of Cancer-Related Cachexia. Curr Oncol Rep. 2017;19(1):3. DOI:10.1007/s11912-017-0562-0bionco.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).]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).]Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. The Anatomical Record. 1940;78(2):149-172. DOI:10.1002/ar.1090780203Hetherington AW, Ranson SW. Hypothalamic lesions and adiposity in the rat. The Anatomical Record. 1940;78(2):149-172. DOI:10.1002/ar.1090780203Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661-671. DOI:10.1038/35007534Schwartz MW, Woods SC, Porte D, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661-671. DOI:10.1038/35007534Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571-578. DOI:10.1038/nn1455Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571-578. DOI:10.1038/nn1455Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol. 2005;184(2):291-318. DOI:10.1677/joe.1.05866Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol. 2005;184(2):291-318. DOI:10.1677/joe.1.05866Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009;2009:141753. DOI:10.1155/2009/141753Austin J, Marks D. Hormonal regulators of appetite. Int J Pediatr Endocrinol. 2009;2009:141753. DOI:10.1155/2009/141753Kalra 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.20.1.0357Kalra 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.20.1.0357Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72-76. DOI:10.1038/29993Kristensen P, Judge ME, Thim L, et al. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature. 1998;393(6680):72-76. DOI:10.1038/29993Upadhya 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.2011.12.004Upadhya 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.2011.12.004Elmquist 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.0801918Elmquist 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.0801918Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr Rev. 2010;31(4):506-543. DOI:10.1210/er.2009-0037Tao YX. The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology. Endocr Rev. 2010;31(4):506-543. DOI:10.1210/er.2009-0037Cummings DE, Schwartz MW. Melanocortins and body weight: a tale of two receptors. Nat Genet. 2000;26(1):8-9. DOI:10.1038/79223Cummings DE, Schwartz MW. Melanocortins and body weight: a tale of two receptors. Nat Genet. 2000;26(1):8-9. DOI:10.1038/79223Herzog 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.2003.08.089Herzog 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.2003.08.089Billington 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.R321Billington 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.R321Ollmann 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.278.5335.135Ollmann 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.278.5335.135Neary 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.xNeary 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.xVan 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.0800792Van 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.0800792Романцова 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:10.14341/2071-8713-4924Романцова 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:10.14341/2071-8713-4924Cinti 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.138.2.4908Cinti 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.138.2.4908Joost HG. Appetite Control. Berlin, Heidelberg: Springer; 2012. DOI:10.1007/978-3-642-24716-3Joost HG. Appetite Control. Berlin, Heidelberg: Springer; 2012. DOI:10.1007/978-3-642-24716-3Friedman 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.xFriedman 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.xSaladin 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:10.1038/377527a0Saladin 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:10.1038/377527a0van 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.2002-0029van 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.2002-0029Tschop 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.50.4.707Tschop 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.50.4.707Tolle 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.2002-020645Tolle 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.2002-020645Nagaya 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/hc4201.097836Nagaya 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/hc4201.097836Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003;9(2):774-778.Shimizu Y, Nagaya N, Isobe T, et al. Increased plasma ghrelin level in lung cancer cachexia. Clin Cancer Res. 2003;9(2):774-778.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.2007-1046Deboer 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.2007-1046DeBoer 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.2007-0016DeBoer 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.2007-0016Garcia 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)71154-4Garcia 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)71154-4Романцова 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).]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).]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.2012.93Hussain 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.2012.93Grossberg AJ, Scarlett JM, Marks DL. Hypothalamic mechanisms in cachexia. Physiol Behav. 2010;100(5):478-489. DOI:10.1016/j.physbeh.2010.03.011Grossberg AJ, Scarlett JM, Marks DL. Hypothalamic mechanisms in cachexia. Physiol Behav. 2010;100(5):478-489. DOI:10.1016/j.physbeh.2010.03.011Petruzzelli M, Wagner EF. Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev. 2016;30(5):489-501. DOI:10.1101/gad.276733.115Petruzzelli M, Wagner EF. Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev. 2016;30(5):489-501. DOI:10.1101/gad.276733.115Anker 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.1998.1446Anker 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.1998.1446Deans 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.0000165004.93707.88Deans 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.0000165004.93707.88Sonti 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.R1394Sonti 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.R1394Plata-Salaman CR. Anorexia induced by activators of the signal transducer gp 130. Neuroreport. 1996;7(3):841-844. DOI:10.1097/00001756-199602290-00038Plata-Salaman CR. Anorexia induced by activators of the signal transducer gp 130. Neuroreport. 1996;7(3):841-844. DOI:10.1097/00001756-199602290-00038Petruzzelli 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.2014.06.011Petruzzelli 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.2014.06.011Larson 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_184Larson 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_184Wolsk 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.00328.2010Wolsk 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.00328.2010Ibebunjo 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.01036-12Ibebunjo 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.01036-12Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16(2):153-166. DOI:10.1016/j.cmet.2012.06.011Fearon KC, Glass DJ, Guttridge DC. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 2012;16(2):153-166. DOI:10.1016/j.cmet.2012.06.011Penna 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:10.1517/14712598.2010.503773Penna 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:10.1517/14712598.2010.503773Fearon 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.2012.209Fearon 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.2012.209Weimann 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.2017.02.013Weimann 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.2017.02.013Хорошилов 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.2018.2.48-52Хорошилов 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.2018.2.48-52Снеговой 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:10.18027/2224-5057-2016-4s2-434-450Снеговой 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

The authors declare that there are no conflicts of interest present.