Melanocortin interventions in cachexia: How soon from bench to bedside?

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 10, Issue 4, 2007, Pages 457-462

  DeBoer, Mark D ^a,b  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

Author keywords

Cachexia; Cytokines; Inflammation; Melanocortin; Pro opiomelanocortin

Indexed keywords

2 [2 [2 (5 BROMO 2 METHOXYPHENYL)ETHYL] 3 FLUOROPHENYL] 4,5 DIHYDRO 1H IMIDAZOLE; AGOUTI RELATED PROTEIN; BLOCKING AGENT; CYTOKINE; EICOSONOIC ACID; GHRELIN; MELANOCORTIN; MELANOCORTIN 4 RECEPTOR; MELANOCORTIN ANTAGONIST; NBI 12I; UNCLASSIFIED DRUG;

CACHEXIA; CANCER; FOOD INTAKE; INFLAMMATION; INTERVENTION STUDY; KIDNEY FAILURE; LEAN BODY WEIGHT; NONHUMAN; REVIEW;

CACHEXIA; CHRONIC DISEASE; HORMONE ANTAGONISTS; HUMANS; MELANOCORTINS; RECEPTORS, MELANOCORTIN;

ANIMALIA;

EID: 34250667431     PISSN: 13631950     EISSN: 15353885     Source Type: Journal    
DOI: 10.1097/MCO.0b013e328108f441     Document Type: Review

References (66)

1. Anker S. Cachexia and cardiology. Circulation 2006; 113:f53-f54.
2. Deans C, Wigmore SJ. Systemic inflammation, cachexia and prognosis in patients with cancer. Curr Opin Clin Nutr Metab Care 2005; 8:265-269.
3. DeBoer MD, Marks DL. Cachexia: lessons from melanocortin antagonism. Trends Endocrinol Metab 2006; 17:199-204.
4. Mak RH, Cheung W, Cone RD, Marks DL. Mechanisms of disease: cytokine and adipokine signaling in uremic cachexia. Nat Clin Pract Nephrol 2006; 2:527-534. This article reviews evidence for the link between inflammation and cachexia, as seen in renal failure.
5. Bossola M, Tazza L, Giungi S, Luciani G. Anorexia in hemodialysis patients: an update. Kidney Int 2006; 70:417-422.
6. Fearon KC, Voss AC, Hustead DS. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr 2006; 83:1345-1350. This article provides excellent insight on the sequelae of cancer cachexia.
7. Shinaberger CS, Kilpatrick RD, Regidor DL, et al. Longitudinal associations between dietary protein intake and survival in hemodialysis patients. Am J Kidney Dis 2006; 48:37-49.
8. Tsai JS, Wu CH, Chiu TY, et al. Symptom patterns of advanced cancer patients in a palliative care unit. Palliat Med 2006; 20:617-622.
9. DeBoer MD, Marks DL. Therapy insight: Use of melanocortin antagonists in the treatment of cachexia in chronic disease. Nat Clin Pract Endocrinol Metab 2006; 2:459-466. This article reviews clinical issues related to cachexia, including difficulties with its treatment.
10. Springer J, Filippatos G, Akashi YJ, Anker SD. Prognosis and therapy approaches of cardiac cachexia. Curr Opin Cardiol 2006; 21:229-233. This article reviews prior attempts to improve cardiac cachexia and additional therapies that hold promise for the future.
11. Tisdale MJ. Clinical anticachexia treatments. Nutr Clin Pract 2006; 21:168-174.
12. Madison LD, Marks DL. Anticatabolic properties of melanocortin-4 receptor antagonists. Curr Opin Clin Nutr Metab Care 2006; 9:196-200. This article provides a comprehensive review of the history of discoveries leading to the unraveling of the melanocortin system and its importance in obesity and cachexia.
13. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci 2005; 8:571-578.
14. Tritos NA, Vicent D, Gillette J, et al. Functional interactions between melanin-concentrating hormone, neuropeptide Y, and anorectic neuropeptides in the rat hypothalamus. Diabetes 1998; 47:1687-1692.
15. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88:131-141.
16. Ollmann MM, Wilson BD, Yang Y-K, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278:135-137.
17. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003; 348:1085-1095.
18. Marks DL, Cone RD. Central melanocortins and the regulation of weight during acute and chronic disease. Recent Prog Horm Res 2001; 56:359-375.
19. Marks DL, Ling N, Cone RD. Role of the central melanocortin system in cachexia. Cancer Res 2001; 61:1432-1438.
20. Cottone S, Palermo A, Vaccaro F, et al. Oxidative stress and inflammation in long-term renal transplanted hypertensives. Clin Nephrol 2006; 66:32-38.
21. Qureshi AR, Alvestrand A, Divino-Filho JC, et al. Inflammation, malnutrition, and cardiac disease as predictors of mortality in hemodialysis patients. J Am Soc Nephrol 2002; 13 (Suppl 1):S28-S36.
22. Jensen PO, Moser C, Kharazmi A, et al. Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia. J Cyst Fibros 2006; 5:145-151.
23. Rao S, Grigg J. New insights into pulmonary inflammation in cystic fibrosis. Arch Dis Child 2006; 91:786-788.
24. Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990; 323:236-241.
25. Satoh S, Oyama J, Suematsu N, et al. Increased productivity of tumor necrosis factor-alpha in helper T cells in patients with systolic heart failure. Int J Cardiol 2006; 111:405-412.
26. Torre-Amione G, Kapadia S, Lee J, et al. Tumor necrosis factor-alpha and tumor necrosis factor receptors in the failing human heart. Circulation 1996; 93:704-711.
27. Abad LW, Schmitz HR, Parker R, Roubenoff R. Cytokine responses differ by compartment and wasting status in patients with HIV infection and healthy controls. Cytokine 2002; 18:286-293.
28. Brabers NA, Nottet HS. Role of the pro-inflammatory cytokines TNF-alpha and IL-1beta in HIV-associated dementia. Eur J Clin Invest 2006; 36:447-458.
29. Aggarwal BB, Shishodia S, Sandur SK, et al. Inflammation and cancer: how hot is the link? Biochem Pharmacol 2006; 72:1605-1621.
30. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2002; 2:862-871.
31. Deli MA, Abraham CS, Kataoka Y, Niwa M. Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol 2005; 25:59-127.
32. Reyes TM, Sawchenko PE. Involvement of the arcuate nucleus of the hypothalamus in interleukin-1-induced anorexia. J Neurosci 2002; 22:5091-5099.
33. McCarthy DO, Kluger MJ, Vander AJ. Effect of centrally administered interleukin-1 and endotoxin on food intake of fasted rats. Physiol Behav 1986; 36:745-749.
34. Uehara A, Sekiya C, Takasugi Y, et al. Anorexia induced by interleukin 1: involvement of corticotropin-releasing factor. Am J Physiol 1989; 257:R613-R617.
35. Scarlett JM, Jobst EE, Enriori PJ, et al. Regulation of central melanocortin signalling by interleukin-1β. Endocrinology 2007 [E-pub ahead of print].
36. Davis TW, Zweifel BS, O'Neal JM, et al. Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. J Pharmacol Exp Ther 2004; 308:929-934.
37. Lundholm K, Daneryd P, Bosaeus I, et al. Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function. Cancer 2004; 100:1967-1977.
38. Lundholm K, Daneryd P, Korner U, et al. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. Int J Oncol 2004; 24:505-512.
39. Cheung W, Yu PX, Little BM, et al. Role of leptin and melanocortin signaling in uremia-associated cachexia. J Clin Invest 2005; 115:1659-1665.
40. Marks DL, Butler AA, Turner R, et al. Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 2003; 144:1513-1523.
41. Joppa MA, Gogas KR, Foster AC, Markison S. Central infusion of the melanocortin receptor antagonist agouti-related peptide (AgRP(83-132)) prevents cachexia-related symptoms induced by radiation and colon-26 tumors in mice. Peptides 2007; 28:636-642. This article provides the first evidence of improved appetite and weight maintenance in an experimental model of radiation-induced cachexia.
42. Joppa MA, Ling N, Chen C, et al. Central administration of peptide and small molecule MC4 receptor antagonists induce hyperphagia in mice and attenuate cytokine-induced anorexia. Peptides 2005; 26:2294-2301.
43. Wisse BE, Frayo RS, Schwartz MW, Cummings DE. Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology 2001; 142:3292-3301.
44. Markison S, Foster AC, Chen C, et al. The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist. Endocrinology 2005; 146:2766-2773.
45. Nicholson JR, Kohler G, Schaerer F, et al. Peripheral administration of a melanocortin 4-receptor inverse agonist prevents loss of lean body mass in tumor-bearing mice. J Pharmacol Exp Ther 2006; 317:771-777. This article demonstrates the effectiveness of ML00253764 when given via intraperitoneal injection.
46. Vos TJ, Caracoti A, Che JL, et al. Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model. J Med Chem 2004; 47:1602-1604.
47. Cheung W, Chen C, Foster A, Marks D, Mak R. Peripheral administration of a novel melanocortin-4-receptor (MC4R) antagonist ameliorates uremia-associated cachexia. In: Pediatric Research: Proceedings and Abstracts of the Pediatric Academic Society; 4-7 May 2006; San Francisco, CA. Philadelphia, PA: Lipincott Williams and Wilkins Philadelphia; 2006: 206.
48. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402:656-660.
49. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346:1623-1630.
50. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature 2001; 409:194-198.
51. Garcia JM, Garcia-Touza M, Hijazi RA, et al. Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia. J Clin Endocrinol Metab 2005; 90:2920-2926.
52. Inui A, Meguid MM. Ghrelin and cachexia. Diabetes Obes Metab 2002; 4:431.
53. Nagaya N, Uematsu M, Kojima M, et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation 2001; 104:1430-1435.
54. Neary NM, Small CJ, Wren AM, et al. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J Clin Endocrinol Metab 2004; 89:2832-2836.
55. Hanada T, Toshinai K, Kajimura N, et al. Anticachectic effect of ghrelin in nude mice bearing human melanoma cells. Biochem Biophys Res Commun 2003; 301:275-279.
56. Wang W, Andersson M, Iresjo BM, et al. Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia. Int J Oncol 2006; 28:1393-1400. This article demonstrates effectiveness of ghrelin in treatment of cachexia and confirms co-expression of the GHS-R in NPY neurons.
57. 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 [E-pub ahead of print]. This article confirms increased expression of AgRP and NPY using ghrelin as a treatment for cancer cachexia.
58. Sun Y, Wang P, Zheng H, Smith RG. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA 2004; 101:4679-4684.
59. Granado M, Priego T, Martin AI, et al. Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am J Physiol Endocrinol Metab 2005; 288:E486-E492.
60. DeBoer MD, Levaseur P, Meguid MM, Suzuki S, Inui A, Taylor J, Halem HA, Dong JZ, Datta R, Culler MD, Marks DL. 2007 Ghrelin improves lean body mass retention in rat models of cachexia: evidence for neuropeptide and anti-inflammatory mechanisms. Program and Abstracts from Endocrine Society 89th Annual Meeting; 2-6 June 2006; Toronto, Canada. Chevy Chase, MD: The Endocrine Society Press; 2006:559.
61. Ramos EJ, Romanova IV, Suzuki S, et al. Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia. Brain Res 2005; 1046:157-164.
62. Barber MD, Ross JA, Voss AC, et al. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br J Cancer 1999; 81:80-86.
63. Bruera E, Strasser F, Palmer JL, et al. Effect of fish oil on appetite and other symptoms in patients with advanced cancer and anorexia/cachexia: a double-blind, placebo-controlled study. J Clin Oncol 2003; 21:129-134.
64. Fearon KC, Barber MD, Moses AG, et al. Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia. J Clin Oncol 2006; 24:3401-3407.
65. Fearon KC, Von Meyenfeldt MF, Moses AG, et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 2003; 52:1479-1486.
66. Moses AW, Slater C, Preston T, et al. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br J Cancer 2004; 90:996-1002.