Obesitiy: Its Complications and Available Medications

Öz

Obesity is one of the common metabolic diseases which is tremendously on the rise. According to the World Health Organization (WHO), the number of patients has increased three times since 1975. A person with Body Mass Index (BMI) equal to or higher than 30.0 is considered obese. Previously considered only as a cosmetic concern, obesity has now been shown to be an aggravating element for various diseases and disorders including diabetes and cardiovascular diseases (CVD). The most common drugs subscribed by physicians include orlistat, rimonabant, liraglutide and sibutramine which have been proven to be effective to reduce body fat in patients. However, in the long run, patients have complained about symptoms which are mild like nausea, insomnia and dizziness to severe complications such as increase in risk of heart attack or stroke. The following review provides insights about synthetic drugs, their classification and their side-effects on human health. Furthermore, a gist of natural products i.e. phytochemicals that can be used as an alternative to these synthetic drugs has also been discussed in the review.

Anahtar Kelimeler

• Obesity,Body Mass Index,Orlistat,Rimonabant,Phytochemicals,Sibutramine

Obezite: Komplikasyonları ve Tedavisinde Kullanılan İlaçlar

Öz

Obezite olağanüstü düzeyde bir atış gösteren yaygın görülen metabolik hastalıklardan biridir. Dünya Sağlık Örgütü'ne (WHO) göre, hasta sayısı 1975'ten bu yana üç kat artmıştır. Beden kitle indeksi (BKİ) 30’a eşit veya 30’dan daha yüksek olan bir kişi obez olarak kabul edilmektedir. Daha önce sadece kozmetik bir sorun olarak kabul edilen obezitenin günümüzde diyabet ve kardiyovasküler hastalıklar (KVH) gibi çeşitli hastalıklar ve bozukluklar için ağırlaştırıcı bir unsur olduğu gösterilmiştir. Doktorlar tarafından en çok reçetelenen ilaçlar olan orlistat, rimonabant, liraglutid ve sibutraminin hastalarda vücut yağ oranını azaltmada etkili oldukları kanıtlanmıştır. Bununla birlikte, uzun vadede hastalar bulantı, uykusuzluk ve baş dönmesi gibi hafif semptomlardan ve kalp krizi veya inme gibi ciddi komplikasyonlardan şikayet etmektedir. Mevcut derleme sentetik ilaçlar, bu ilaçların sınıflandırılması ve insan sağlığı üzerindeki yan etkileri hakkında bilgi vermektedir. Ek olarak, bu sentetik ilaçlara alternatif olarak kullanılabilecek doğal ürünler olan fitokimyasalların bir özeti de mevcut derlemede tartışılmıştır.

Anahtar Kelimeler

• Beden kitle indeksi,obezite,orlistat,sibutramin,fitokimyasallar,rimonabant

Kaynakça

1. Ng M, Fleming T, Robinson M. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766-781.
2. Pi-Sunyer X. The medical risks of obesity. Postgrad Med J. 2009;121(6):21-33.
3. Lobstein T, Baur L, Uauy R. IASO International obesity task force. Obesity in children and young people: a crisis in public health. Obesity Rev. 2004;1:4–104.
4. Kalra S, Unnikrishnan AG. Obesity in India: The weight of the nation. J Med Nutr Nutraceutic. 2012;1:37-41.
5. Yang JY, Della-Fera MA, Hartzell DL, Nelson-Dooley C, Hausman DB, Baile CA. Esculetin Induces Apoptosis and inhibits adipogenesis in 3T3‐L1 cells. Obesity. 2006;14:1691-1699.
6. Chris B. The changing face of malnutrition, IFPRI Forum, International Food Policy Research Institute, Washington 2004.
7. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Intl J Epidem. 2006;36:220–225.
8. Misra A, Khurana L. Obesity related noncommunicable diseases: South Asians vs White Caucasians. Intl J Obesity (Lond). 2011;35:167–187.

9. Kaur P, Rao SR, Radhakrishnan E, Rajasekar D, Gupte MD. Prevalence, awareness, treatment, control and risk factors for hypertension in a rural population in South India. Intl J Pub Health. 2012;57:87–94.
10. Alberti KGMM, Eckel RH, Grundy SM et al. Harmonizing the Metabolic Syndrome: A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–1645.
11. Buttriss J. Adverse Reactions to Food. The Report of a British Nutrition Foundation Task Force. 1th ed. Oxford: Blackwell Science Ltd.; 1999.
12. Hall JE, Crook ED, Jones DW, Wofford MR, Dubbert PM. Mechanisms of obesity-associated cardiovascular and renal disease. Am J Med Sci. 2002;324(3):127–137.
13. Jones DW, Kim JS, Andrew ME. Body mass index and blood pressure in Korean men and women: the Korean National Blood Pressure Survey. J Hypertens. 1994; 12:1433-1437. doi:10.1097/00004872-199412000-00018
14. Stevens VJ, Obarzanek E, Cook NR, Lee I, Appel LJ, Smith West D. Long-term weight loss and changes in blood pressure: results of the trials of hypertension prevention, Phase II. J Cardiopulm Rehab. 2011;21(3):176-179. doi:10.1097/00008483-200105000-00013
15. Kasuga M. Insulin resistance and pancreatic beta cell failure. J Clin Invest. 2006; 116(7):1756-1760.
16. Reilly JJ, Kelly J. Long-term impact of overweight and obesity in childhood and adolescence on morbidity and premature mortality in adulthood: systematic review. Int J Obesity. 2011;35(7):891–898.
17. Juonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA. Childhood Adiposity, Adult Adiposity, and Cardiovascular Risk Factors. New Eng J Medicine. 2011;365(20):1876–1885.
18. Reijman M, Pols HA, Bergink AP, Hazes JM, Belo JN, Lievense AM et al. Body mass index associated with onset and progression of osteoarthritis of the knee but not of the hip: the Rotterdam Study. Ann rheum dis. 2006;66(2):158-162.
19. Rajgopal R, Martin R, Howard JL, Somerville L, MacDonald SJ, Bourne R. Outcomes and complications of total hip replacement in super-obese patients. Bone& Joint J. 2013: 95-B(6):758–763.
20. Romero-Corral A, Caples SM, Lopez-Jimenez F, Somers VK. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest. 2010;137(3): 711-719.
21. Kolb R, Sutterwala FS, Zhang W. Obesity and cancer: inflammation bridges the two. Curr Op Pharmacol. 2016;29:77-89.
22. Allott EH, Hursting SD. Obesity and cancer: mechanistic insights from transdisciplinary studies. Endocrine-related cancer. 2015;22(6):R365-86.
23. Stafford RS, Radley DC. National Trends in Antiobesity Medication Use. Arch Intern Med. 2003;163(9):1046–1050.
24. Li MF, Cheung BM. Rise and fall of anti-obesity drugs. World J Diabetes. 2011;2(2): 19–23. doi:10.4239/wjd.v2.i2.19
25. Cheung BM, Cheung TT, Samaranayake NR. Safety of antiobesity drugs. Ther A Drug Safety. 2013;4(4):171–181. doi:10.1177/2042098613489721
26. Mohamed GA, Ibrahim SRM, Elkhayat ES, el Dine RSE. Natural anti-obesity agents. Bull Faculty Pharm, Cairo University. 2014;52(2):269-284.
27. https://www.drugbank.ca/ Accessed August 12, 2019.
28. Guerciolini R. Mode of action of orlistat. Int J Obes Relat Metab Disord. 1997;21(Suppl 3):S12–S23
29. Xiguang Qi. IOP Conf. Ser. Mater Sci Eng. 2018; 301 012063
30. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9653):1906-1913. doi:10.1016/S0140-6736(08)61525-1
31. https://contrave.com/ Accessed November 23, 2019.
32. https://zafgen.gcs-web.com Accessed November 23, 2019.
33. Han LK, Kimura Y, Okuda H. Anti-obesity effects of natural products. Stud Nat Prod Chem. 2005;30:79–110.
34. Yamamoto M, Shimura S, Itoh Y, Ohsaka T, Egawa M. Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet. Int J Obes Relat Metab Disord. 2000;24:758–764.
35. Handa T, Yamaguchi K, Sono Y, Yazawa K. Effects of fenugreek seed extract in obese mice fed a high-fat diet. Biosci Biotechnol Biochem. 2005;69:1186–1188.
36. Han LK, Sumiyoshi M, Zhang J, Liu MX, Zhang XF. Anti-obesity action of Salix matsudana leaves (Part 1). Antiobesity action by polyphenols of Salix matsudana in high fat-diet treated rodent animals. Phytother Res. 2003;17:1188–1194.
37. Moreno DA, Ilic N, Poulev A, Brasaemle DL, Fried SK. Inhibitory effects of grape seed extract on lipases. Nutrition. 2003;19:876–879.
38. Ninomiya K, Matsuda H, Shimoda H, Nishida N, Kasajima N. Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett. 2004;14:1943–1946.
39. Hatano T, Yamashita A, Hashimoto T, Ito H, Kubo N. Flavan dimers with lipase inhibitory activity from Cassia nomame. Phytochemistry. 1997;46:893–900.
40. Shimada T, Hiramatsu N, Kasai A, Mukai M, Okamura M. Suppression of adipocyte differentiation by Cordycepsmilitaris through activation of the aryl hydrocarbon receptor. Am J Physiol Endocrinol Metab. 2008;295:E859–867.
41. Gades MD, Stern JS. Chitosan supplementation and fecal fat excretion in men. Obes Res. 2003;11:683–8.
42. Kitahara M, Asano M, Naganawa H, Maeda K, Hamada M. Valilactone, an inhibitor of esterase, produced by actinomycetes. J Antibiot. 1987;40:1647–1650.
43. Husain GM, Chatterjee SS, Singh PN, Kumar V. Hypolipidemic and antiobesity-like activity of standardized extract of Hypericum perforatum L. in rats. ISRN Pharmacol. 2011;2011:505247. doi: 10.5402/2011/505247.
44. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, et al. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci. 2005;97:124–131.
45. Awad AB, Begdache LA, Fink CS. Effect of sterols and fatty acids on growth and triglyceride accumulation in 3T3-L1 cells. J Nutr Biochem. 2000;11:153–158.
46. Kim MS, Kim JK, Kwon DY, Park R. Anti-adipogenic effects of Garcinia extract on the lipid droplet accumulation and the expression of transcription factor. Biofactors. 2004;22:193–196.
47. Moon HS, Lee HG, Choi YJ, Kim TG, Cho CS. Proposed mechanisms of ()-epigallocatechin-3-gallate for anti-obesity. Chem Biol Interact. 2007;167:85–98.
48. Ejaz A, Wu D, Kwan P, Meydani M. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. J Nutr. 2009;139:919–925.
49. Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother Res. 2009; 23:262–266.
50. Ambati S, Yang JY, Rayalam S, et al. Ajoene exerts potent effects in 3T3-L1 adipocytes by inhibiting adipogenesis and inducing apoptosis. Phytother Res.2009; 23:513–518.
51. MacLean DB, Luo LG. Increased ATP content/production in the hypothalamus may be a signal for energy-sensing of satiety: studies of the anorectic mechanism of a plant steroidal glycoside. Brain Res. 2004;1020:1–11.
52. Yang JY, Della-Fera MA, Nelson-Dooley C, Baile CA. Molecular mechanisms of apoptosis induced by ajoene in 3T3-L1 adipocytes. Obes Res. 2006;14:388–397.