Pooja K. JOSHİ, Rinkey A. CHAWLA, Dhruti H. MİSTRY, Meonis A. PİTHAWALA

Obesity -"An excuse or a blame"

On a global scale, obesity has reached epidemic proportions and is a major contributor to the global burden of chronic disease and disability. At the moment, more than one billion adults worldwide are overweight and at least 300 million of them are clinically obese. Obesity is a rising worldwide problem affecting both the developed countries as well as the developing nations. Obesity is common but complex and multifactorial disorder with higher heritability. Obesity results because of body fat accumulated over a time because of chronic energy imbalance that is calories consumed exceed calories expended. There are many genetic and environmental factors that influence this balance. Obesity is an important public health problem because it increases the risk of developing diabetes, hypertension, heart disease and some type of cancers. The present article reviews role of genes that are identified in causing obesity.

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1. Quinn P. Stein, MS, CGC; Amelia R. Mroch, MS, CGC; Kristen L De Berg, MS; Jason D. Flanagan, MS, CGC. The Influential Role of Genes in Obesity 2011.

2. Deurenberg P, Weststrate JA, Seidell JC. Body mass index as a measure of body fatness: age-and sex-specific prediction formulas. Br J Nutrition 1991; 65: 105-114.

3. French SA, Story M, Jeffery RW. Environmental influences on eating and physical activity. Annu Rev Public Health 2001; 22: 309-335.

4. Bell CG, Walley AJ, Froguel P. The genetics of human obesity. Nat Rev Genet 2005; 6: 221-234.

5. Bouchard C. Current understanding of the etiology of obesity: genetic and nongenetic factors. Am J Clin Nutr 1991; 53: 1561-1565.

6. Allison DB, Faith MS, Nathan JS. Risch's lambda values for human obesity. Int J Obes Relat Metab Disord 1996; 20: 990-999.

7. Gallagher D, Heymsfield SB, Heo M, et al. Healthy percentage body fat ranges: an approach for developing guidelines based on body mass index. Am J Clin Nutr 2000; 72: 694-701.

8. WHO 2000 p.9 http://en.wikipedia.org/wiki/Classification_of_o besity#cite_note-13)

9. Bray GA. Contemporary diagnosis and management of obesity. Handbooks in Health Care Co, Newtown, PA 1998.

10. Campfield, LA, Brandon P, Smith FJ. On-line continuous measurement of blood glucose and meal pattern in free-feeding rats; the role of glucose in meal initiation. Brain Res Bull 1985; 14: 605.

11. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normalweight and obese humans. N Engl J Med 1996; 344: 292.

12. Bray GA, York DA. Leptin and clinical medicine: a new piece in the puzzle of obesity. J Clin Endocrinol Metab 1997; 82: 2771.

13. 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.

14. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.

15. Druce MR, Wren AM, Park AJ, et al. Ghrelin increases food intake in obese as well as lean subjects. Int J Obes Relat Metab Disord 2005; 29: 1130.

16. Barrachina MD, Martinez V, Wang L, et al. Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice. Proc Natl Acad Sci USA 1997; 94: 10455.

17. Erlanson-Albertsson C, York D. Enterostatin a peptide regulating fat intake. Obes Res 1997; 5: 360.

18. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003; 349: 941.

19. Berthoud HR. Multiple neural systems controlling food intake and body weight. Neurosci Biobehav Rev 2002; 26: 393.

20. Vassallo J, Pathogenesis of obesity. Journal of the Malta College of Pharmacy Practice 2007.

21. Tataranni PA, Young JB, Bogardus C, Ravussin E. A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. Obes Res 1997; 5: 341.

22. Kelly Evelyn KB. Obesity. Wesport, Connecticut: Greenwood Press (2006).

23. Al Rubeaan K. New candidate obesity genes. In K. Keller (Ed.), Encyclopedia of obesity. Thousand Oaks, CA: SAGE Publications, (2008) pp. 496-497.

24. Neel JV. Diabetes mellitus: a ,,thrifty" genotype rendered detrimental by "progress". Am J Hum Genet 1962; 14: 353-362.

25. Harsch I. (ed.). The various types and treatments for obesity. New York: Nova Science Publishers (2006).

26. Katsuki A, Sumida Y, Gabazza EC, et al. Plasma levels of agouti-related protein are increased in obese men. J Clin Endocrinol Metab 2001; 86: 1921.

27. Nagle DL, McGrail SH, Vitale J, et al. The mahogany protein is a receptor involved in suppression of obesity. Nature 1999; 398: 148.

28. Zhang YY, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homolog. Nature 1994; 372: 425.

29. Campfield LA, Smith FJ, Burn P. The OB protein (leptin) pathway a link between adipose tissue mass and central neural networks. Horm Metab Res 1996; 28: 619.

30. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387: 903.

31. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 1999; 341: 879.

32. Considine RV, Considine EL, Williams CJ, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 1995; 95: 2986.

33. Clement K, Vaisse C, Lahlou N, et al. A mutation in the leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392: 398.

34. 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.

35. Chen AS, Marsh DJ, Trumbauer ME, et al. Inactivation of the mouse melanocortin-3 receptor results in increased fat mass and reduced lean body mass. Nat Genet 2000; 26: 97.

36. Lucas JJ, Yamamoto A, Scearce-Levie K, et al. Absence of fenfluramine-induced anorexia and reduced c-fos induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice. J Neurosci 1998; 18: 5537.

37. Stunkard AJ, Harris JR, Pedersen NL, McLearn GE. The body-mass index of twins who have been reared apart. N Engl J Med 1990; 322: 1483.

38. Centers for Disease Control and Prevention CDC 24/7: Saving Lives Protecting People.TM Genomics and Health http://www.cdc.gov/genomics/resources/diseas es/obesity/obesedit.htm

39. Banks WA, Kastin AJ, Huang WT, Jaspan JB, Maness LM. Leptin enters the brain by a saturable system independent of insulin. Peptides 1996; 17: 305-311.

40. Wang Q, Bing C, Al-Barazanji K, et al. Interactions between leptin and hypothalamic neuropeptide Y neurons in the control of food intake and energy homeostasis in the rat. Diabetes 1997; 46: 335-341.

41. Claycombe KJ, Xue BZ, Mynatt RL, Zemel MB, Moustaid-Moussa N. Regulation of leptin by agouti. Physiol Genomics 2000; 2: 101-105.

42. Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001; 411: 480-484.

43. Roffey DM, Ashdown LC, Dornan HD, et al. Pilot evaluation of multidisciplinary,medically supervised,non surgrical weight loss programme on the severity of low back pain in obese adults. Spine J 2011; 11: 197-204.

44. Jiang L, Rong J, Wang Y, et al. The relationship between body mass index and hip osteoarthritis: A systematic review and meta analysis. Joint bone spine 2011; 78: 150-155.

45. Malnick SD, Knobler H. The medical complications of obesity. QJM 2006; 99: 565-579.

46. Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Pathogenesis and treatment. Lancet 2008; 371: 2153-2156.

47. Wofford MR, Hall JE. Pathophysiology and treatment of obesity hypertension. Currpharm Des 2004; 10: 3621-2637.

48. Alpert ME. Obesity cardiomayopathy: Pathophysiology and evolution of clinical syndrome. Am J Med Sci 2001; 321: 225-236.

49. Hajer GR, van Haften TW, Visseren FLJ. Adipose tissue dysfunction in obesity, diabetes and vascular disease. Eur Heart J 2008; 29: 2959- 2971.

50. Hatley L, Pris JB. Fat as an endocrine organ: relationship to the metabolic syndrome Am J Med Sci 2005; 330: 280-289.

51. Sharma V, McNeill JH. The emerging roles of leptin and Ghrelin in cardiovascular physiology and pathophysiology. Curr Vasc Pharmacol 2005; 3: 169-180.

52. Guha PK, Villarreal D, Reams GP, Freeman RH. Role of leptin in regulation of body fluid volume and pressure. Am J Ther 2003; 10: 211-218.

53. Kshatriya S, Liu K, Salah A, et al. Obesity hypetension: the regulatory role of leptin. Int J Hypertens 2011.

54. Boden G, Lebed B, Schatz M, Homko C, Lemieux S. Effects of acute changes of plasma free fatty acid on intramyocellular fat content and insulin resistance in healthy subjects. Diabetes 2001; 50: 1612-1617.

55. Marchesini G, Brizi M, Bianchi G, et al. Noon alcoholic fatty liver disease: A feature of the metabolic syndrome. Diabetes 2001; 50: 1844- 1850.

56. Ravussin E, Smith SR. Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insukin resistance, Type 2 diabetes mellitus. Ann N Y Acad Sci 2002; 967: 363-378.

57. Schaffer JE. Lipotoxicity when tissue over eat. Curr Opin Lipidol 2003; 14: 281-287.

58. Marinou K, Tousoulis D, Antonopoulos AS, Stefanadi E, Stefanadis C. Obesity and cardiovascular disease: from pathophysiology to risk stratification. Int J Cardiol 2010; 1: 76-88.

59. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss J Am College Cardiol 2009; 53: 1925-1932.

60. Messereli FH, Nunez BD, Ventura HO, Snyder DW. Over weight and sudden death: increased ventricular ectopy in cardiomayopathy of obesity. Arch Intern Med 1987; 147: 1725-1728.

61. Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the framinghan study. Am Heart J 1988; 115: 869-875.

62. Reaven GM. The metabolic syndrome: time to get off the merry-go-round? J Intern Med 2011; 269: 127-136.

63. Visioli F. Metabolic syndrome: When nutrition helps pharma. Eur J Pharmacol 2011; 668: 5.

64. Bethesda MD. Third report of National cholesterol education programme (NCEP) Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatmen panel III). Ntional institutes of health; 2002.

65. Piper AJ. Obesity hypoventilation syndrome - the big and the breathless. Sleep Med Rev 2011; 15: 79-89.

66. Poulain M, Doucet M, Major GC, et al. The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. CMAJ 2006; 174: 1293-1299.

67. Kuo LC, Polson AM, Kang T. Associations between periodontal diseases and systemic diseases: a review of the inter-relationships and interactions with diabetes, respiratory diseases, cardiovascular diseases and osteoporosis. Public Health 2008; 122: 417-433.

68. World Health Report. Reducing risks,promoting healthy life; 2002.

69. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancerrisk and progression. Endocr Relat Cancer 2007; 14: 189-206.

70. Cottam D, Fisher D, Ziemba A, et al. Tumor growth factor expression in obesity and changes in expression with weight loss: another cause of increased virulence and incidents of cancer in obesity. Surg Obes Relat Dis 2010; 6: 538-541.

71. Xu Q, Anderson D, Lurie-Beck J. The relationship between abdominal obesity and depression in the general population; systematic review and meta analysis. Obes Res Clin Pract 2011; 5: 267-278.

72. International Obesity Task Force (IOTF) http://www.iotf.org/.

73. Profenno LA, Porsteinsson AP, Faraone SV. Meta analysis of alzhimers's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry 2011; 67: 505-512.

74. Mazza M, Marano G, Traversi G, Briap, Mazza S. Primary cerebral blood flow deficiency and alzhi,er;s disease: shadows and lights. J Alzhimer Dis 2011; 23: 375-389.

75. Kellen L, Xu W, Wang HX, Winbald B, Fratiglioni L, Graff C. The obesity related gene, FTO, interacts with APOE, and is associated with alzhimer's disease risk: a prospective cohort study. J Alzhimer Dis 2011; 23: 461-469.

76. Nicole Lopes, "Current Connections between Genetics and Obesity" (April 7, 2009). Undergraduate Library Research Award. Paper 2. http://digitalcommons.lmu.edu/ulra/awards/20 09/2