Skip to main content
SpringerLink
Log in

Genetic aspects of susceptibility to obesity and related dyslipidemias

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Obesity has a multifactorial origin. However, although environmental variables undoubtedly play a role in the development of obesity, it is now clear that genetic variation is also involved in the determination of an individual's susceptibility to body fat accumulation. In addition, it is also widely accepted that obesity is not a single homogeneous phenotype. It is also heterogeneous regarding its causes and metabolic complications. The regional distribution of body fat appears to be an important correlate of the metabolic complications that have been related to obesity. Due to their higher accumulation of abdominal fat, men are generally more at risk for the metabolic complications of obesity than women whereas some obese women, with large gluteal-femoral adipose depots may have a cosmetic problem which may not necessarily require medical intervention. Several studies have been conducted to understand the mechanisms by which abdominal obesity is related to diabetes, hypertension and cardiovascular disease. It appears that the increased risk of abdominal obesity is the result of complex hormonal and metabolic interactions. Studies in genetic epidemiology have shown that both total body fatness and the regional distribution of body fat have a significant genetic component. Standardized intervention studies using an identical twin design have shown that individuals that have the same genetic background tend to show similar changes in body fat and in plasma lipoprotein levels when exposed to standardized caloric excess or energy restriction. Finally, although abdominal obesity is a significant risk factor for cardiovascular disease, not every abdominal obese subject will experience metabolic complications, suggesting that some obese individuals may be more susceptible than others. Variation in several genes relevant to lipid and lipoprotein metabolism may alter the relation of abdominal obesity to dyslipoproteinemias. Abdominal obesity should therefore be considered as a factor that exacerbates an individual's susceptibility to cardiovascular disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bouchard C: Current understanding of the etiology of obesity: Genetic and nongenetic factors. Am J Clin Nutr 53: 1561S-1565S, 1991

    Google Scholar 

  2. Ernsberger P, Askew P: Health implications of obesity: An alternative view. J Obes Weight Regul 6: 58–137, 1987

    Google Scholar 

  3. National Institutes of Health Consensus Development Panel on the Health Implications of Obesity: Health implications of obesity: National Institutes of Health Consensus Development Conference Statement. Ann Intern Med 103: 1073–1077, 1985

    Google Scholar 

  4. Kissebah AH, Freedman DS, Peiris AN: Health risk of obesity. Med Clin North Amer 73: 111–138, 1989

    Google Scholar 

  5. Kissebah AH, Peiris AN: Biology of regional body fat distribution: Relationship to non-insulin-dependent diabetes mellitus. Diabetes Metab Rev 5: 83–109, 1989

    Google Scholar 

  6. Després JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A, Bouchard C: Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis 10: 497–511, 1990

    Google Scholar 

  7. Larsson B, Björntorp P, Tibblin G: The health consequences of moderate obesity. Int J Obesity 5: 97–116, 1981

    Google Scholar 

  8. Hubert HB, Feinleib M, McNamara PM, Castelli WP: Obesity as an independent risk factor for cardiovascular disease: A 26-year follow-up of participants in the Framingham Heart Study. Circulation 67: 968–977, 1983

    Google Scholar 

  9. Manson JE, Colditz GA, Stampfer MJ, et al.: A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 322: 882–889, 1990

    Google Scholar 

  10. Bray GA, Gray DS: Treatment of obesity: An overview. Diabetes Metab Rev 4: 653–679, 1988

    Google Scholar 

  11. Bouchard C, Després JP: Variation in fat distribution with age and health implications. In: Eckert HM, Spirduso W (eds.) Physical activity and aging. American Academy of Physical Education, 1989, pp 78–106

  12. Björntorp P: Hazards in subgroups of human obesity. Eur J Clin Invest 14: 239–241, 1984

    Google Scholar 

  13. Harrison GH: Height-Weight tables. Ann Intern Med 103: 989–994, 1985

    Google Scholar 

  14. Vague J: La différentiation sexuelle, facteur déterminant des formes de l'obésité. Presse Med 30: 339–340, 1947

    Google Scholar 

  15. Vague J: The degree of masculine differentiation of obesities: A factor determining predisposition to diabetes, atherosclerosis, gout and uric-calculous disease. Am J Clin Nutr 4: 20–34, 1956

    CAS  PubMed  Google Scholar 

  16. Larsson B, Svardsudd K, Welin L, Wilhemsen L, Björntorp P, Tibblin G: Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13 year follow-up of participants in the study of men born in 1913. Br Med J 288: 1401–1404, 1984

    Google Scholar 

  17. Lapidus L, Bengtsson C, Larsson B, Penncrt K, Rybo E, Sjöström L: Distribution of adipose tissue and risk of cardiovascular disease and death: A 12 year follow-up of participants in the population study of women in Gothenburg, Sweden. Br Med J 289: 1261–1263, 1984

    Google Scholar 

  18. Stokes J III, Garrison RJ, Kannel WB: The independent contributions of various indices of obesity to the 22-year incidence of coronary heart disease: The Framingham heart study. In: Vague J, Björntop P, Guy-Grand B, Rebuffé-Scrive M, Vague P (eds.) Metabolic complications of human obesities. Elsevier, Amsterdam, 1985, pp 49–57

    Google Scholar 

  19. Ducimetière P, Richard J, Cambien F: The pattern of subcutaneous fat distribution in middle-aged men and the risk of coronary heart disease: The Paris Prospective Study. Int J Obesity 10: 229–240, 1986

    Google Scholar 

  20. Donahue RP, Abbott RD, Bloom E, Reed DM, Yano K: Central obesity and coronary heart disease in men. Lancet i: 822–824, 1987

    Google Scholar 

  21. Björntorp P: Abdominal obesity and the development of noninsulin dependent diabetes mellitus. Diabetes Metab Rev 4: 615–622, 1988

    Google Scholar 

  22. Björntorp P: ‘Portal’ adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10: 493–496, 1990

    Google Scholar 

  23. Després JP: Obesity and lipid metabolism: Relevance of body fat distribution. Curr Op Lipidol 2: 5–15, 1991

    Google Scholar 

  24. Bouchard C, Bray GA, Hubbard VS: Basic and clinical aspects of regional fat distribution. Am J Clin Nutr 52: 946–950, 1990

    Google Scholar 

  25. Després JP: Lipoprotein metabolism in abdominal obesity. In: Oomura Y, et al. (eds.) Progress in obesity research 1990. John Libbey, London, 1991, pp 285–290

    Google Scholar 

  26. Després JP, Allard C, Tremblay A, Talbot J, Bouchard C: Evidence for a regional component of body fatness in the association with serum lipids in men and women. Metabolism 34: 967–973, 1985

    Google Scholar 

  27. Després JP, Tremblay A, Pérusse L, Leblanc C, Bouchard C: Abdominal adipose tissue and serum HDL-cholesterol: Association independent from obesity and serum triglyceride concentration. Int J Obes 12: 1–13, 1988

    Google Scholar 

  28. Després JP, Tremblay A, Bouchard C: Regional adipose tissue distribution and plasma lipoproteins. In: Bouchard C, Johnston FE (eds.) Fat distribution during growth and later health outcomes. Alan R. Liss, New York, 1988, pp 221–241

    Google Scholar 

  29. Després JP, Moorjani S, Tremblay A et al.: Relation of high plasma triglyceride levels associated with obesity and regional adipose tissue distribution to plasma lipoprotein-lipid composition in premenopausal women. Clin Invest Med 12: 374–380, 1989

    Google Scholar 

  30. Terry RB, Wood PD, Haskell WL, Stefanick ML, Krauss RM: Regional adiposity pattern in relation to lipids, lipoprotein cholesterol, and lipoprotein subfraction mass in men. J Clin Endocrinol Metab 68: 191–199, 1989

    Google Scholar 

  31. Harris-Peeples L, Carpenter JW, Israel RG, Barakat HA: Alterations in low-density lipoproteins in subjects with abdominal obesity. Metabolism 38: 1029–1036, 1989

    Google Scholar 

  32. Kalkhoff RK, Hartz AH, Rupley D, Kissebah AH, Kelber S: Relationship of body fat distribution to blood pressure, carbohydrate tolerance, and plasma lipids in healthy obese women. J Lab Clin Med 102: 621–627, 1983

    Google Scholar 

  33. Krotkiewski M, Björntorp P, Sjöström L, Smith U: Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest 72: 1150–1162, 1983

    Google Scholar 

  34. Evans DJ, Hoffman RG, Kalkhoff RK, Kissebah AH: Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism 33: 68–75, 1984

    Google Scholar 

  35. Raison J, Basdevant A, Guy-Grand B: Relation entre la réparti-tion du tissu adipeux et les lipides circulants chez la femme obèse. Presse Med 16: 431–433, 1987

    Google Scholar 

  36. Anderson AJ, Sobocinski KA, Freedman DS, Barboriak JJ, Rimm AA, Gruchow HW: Body fat distribution, plasma lipids and lipoproteins. Arteriosclerosis 8: 88–94, 1988

    Google Scholar 

  37. Haffner SM, Stern MP, Hazuda HP, Pugh JA, Patterson JK: Do upper-body and centralized adiposity measure different aspects of regional body-fat distribution? Relationship to non-insulin dependent diabetes mellitus, lipids, and lipoproteins. Diabetes 36: 43–51, 1987

    Google Scholar 

  38. Fujioka S, Matsuzawa Y, Tokunaga K, Tarui S: Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 36: 54–59, 1987

    Google Scholar 

  39. Sparrow D, Borkan GA, Gerzof SG, Wisniewski C, Silbert CK: Relationship of body fat distribution to glucose tolerance. Results of computed tomography in male participants of the normative aging study. Diabetes 35: 411–415, 1986

    Google Scholar 

  40. Després JP, Nadeau A, Tremblay A et al.: Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 38: 304–309, 1989

    Google Scholar 

  41. Després JP, Moorjani S, Ferland M et al.: Adipose tissue distribution and plasma lipoprotein levels in obese women: Importance of intra-abdominal fat. Arteriosclerosis 9: 203–210, 1989

    Google Scholar 

  42. Després JP. Lipoprotein metabolism in visceral obesity. Int J Obesity 15: 45–52, 1991

    Google Scholar 

  43. Nikkila EA, Taskinen MR, Sane T: Plasma high-density lipoprotein concentration and subfraction distribution in relation to triglyceride metabolism. Am Heart J 113: 543–548, 1987

    Google Scholar 

  44. Eisenberg S: High density lipoprotein metabolism. J Lipid Res 25: 1017–1058, 1984

    Google Scholar 

  45. Després JP, Ferland M, Moorjani S et al.: Role of hepatictriglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. Arteriosclerosis 9: 485–492, 1989

    Google Scholar 

  46. Després JP, Moorjani S, Pouliot MC et al.: Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women. Metabolism 39: 577–583, 1990

    Google Scholar 

  47. Björntorp P: Obesity and the risk of cardiovascular disease. Ann Clin Res 17: 3–9, 1985

    Google Scholar 

  48. Björntorp P: Possible mechanisms relating fat distribution and metabolism. In: Bouchard C, Johnston FE (eds.) Fat distribution during growth and later health outcomes. Alan R. Liss, Inc, 1988, pp 175–191

  49. Kissebah AH, Evans DJ, Peiris A, Wilson CR: Endocrine characteristics in regional obesities: Role of sex steroids. In: Vague J, Björntorp P, Guy-Grand B, Rebuffé-Scrive M, Vague P (eds.) Metabolic complications of human obesities. Elsevier, Amsterdam, 1985, pp 115–130

    Google Scholar 

  50. Kissebah AH, Peiris AN, Evans DJ: Mechanisms associating body fat distribution to glucose intolerance and diabetes mellitus: Window with a view. Acta Med Scand 5723: 79–89, 1988

    Google Scholar 

  51. Howard BV: Lipoprotein metabolism in diabetes mellitus. J Lipid Res 28: 613–628, 1987

    CAS  PubMed  Google Scholar 

  52. Ferland M, Després JP, Nadeau A et al.: Contribution of glucose tolerance and plasma insulin levels to the relationships between body fat distribution and plasma lipoprotein levels in women. Int J Obesity 15: 677–688, 1991

    Google Scholar 

  53. Laakso M, Sarlund H, Mykkänen L: Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance. Arteriosclerosis 10: 223–231, 1990

    Google Scholar 

  54. Evans DJ, Hoffman RG, Kalkhoff RK, Kissebah AH: Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. J Clin Endocrinol Metab 57: 304–310, 1983

    Google Scholar 

  55. Peiris AN, Mueller RA, Struve MF, Smith GA, Kissebah AH: Relationship of androgenic activity to splanchnic insulin metabolism and peripheral glucose utilization in premenopausal women. J Clin Endocrinol Metab 64: 162–169, 1987

    Google Scholar 

  56. Tikkanen MJ, Nikkila EA: Regulation of hepatic lipase and serum lipoproteins by sex steroids. Am Heart J 113: 562–567, 1987

    Google Scholar 

  57. Applebaum-Bowden D, Haffner SM, Hazzard WR: The dyslipoproteinemia of anabolic steroid therapy: Increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein cholesterol. Metabolism 36: 949–952, 1987

    Google Scholar 

  58. Rebuffé-Scrive M: Steroid hormones and distribution in adipose tissue. Acta Med Scand S23: 143–146, 1988

    Google Scholar 

  59. Rebuffé-Scrive M, Krotkiewski M, Elfverson J, Björntorp P: Muscle and adipose tissue morphology and metabolism in Cushing's syndrome. J Clin Endocrinol Metab 67: 1122–1128, 1988

    Google Scholar 

  60. Brindley DN, Rolland Y: Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis. Clin Sci 77: 453–461, 1989

    Google Scholar 

  61. Leibel RL, Edens NK, Fried SK: Physiologic basis for the control of body fat distribution in humans. Ann Rev Nutr 9: 417–443, 1989

    Google Scholar 

  62. Rebuffé-Scrive M, Enk L, Crona N et al.: Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation. J Clin Invest 75: 1973–1976, 1985

    Google Scholar 

  63. Smith U, Hammersten J, Björntorp P, Kral JG: Regional differences and effect off weight reduction on human fat cell metabolism. Eur J Clin Invest 9: 327–332, 1979

    Google Scholar 

  64. Lafontan M, Dang-Trap L, Berlan M: Alpha-adrenergic antilipolytic effect of adrenaline in human fat cells of the thigh: Comparison with adrenaline responsiveness of different fat deposits. Eur J Clin Invest 9: 261–266, 1978

    Google Scholar 

  65. Mauriège P, Després JP, Marcotte M et al.: Abdominal fat cell lipolysis, body fat distribution, and metabolic variables in premenopausal women. J Clin Endocrinol Metab 71: 1028–1035, 1990

    Google Scholar 

  66. Pouliot MC, Després JP, Moorjani S et al.: Regional variation in adipose tissue lipoprotein lipase activity: Association with plasma high density lipoprotein levels. Eur J Clin Invest 21: 398–405, 1991

    Google Scholar 

  67. Kaplan NM: The deadly quartet. Upper body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Arch Intern Med 149: 1514–1520, 1989

    Article  CAS  PubMed  Google Scholar 

  68. Bouchard C: Genetics of body fat, energy expenditure, and adipose tissue metabolism. In: EM Berry, SH Blondheim, HE Eliahou, et al. (eds.) Recent advances in obesity research V, John Libbey, London, 1987, pp 16–25

    Google Scholar 

  69. Bouchard C: Inheritance of human fat distribution. In: C Bouchard, FE Johnston (eds.) Fat distribution during growth and later health outcomes. Alan R Liss, New York, 1988, pp 103–125

    Google Scholar 

  70. Bouchard C: Genetic factors in obesity. Med Clin North Amer 73: 67–81, 1989

    Google Scholar 

  71. Bouchard C, Savard R, Després JP et al.: Body composition in adopted and biological siblings. Hum Biol 57: 61–75, 1985

    Google Scholar 

  72. Bouchard C, Pérusse L: Heredity and body fat. Ann Rev Nutr 8: 259–277, 1988

    Google Scholar 

  73. Bouchard C, Pérusse L, Leblanc C et al.: Inheritance of the amount and distribution of human body fat. Int J Obesity 12: 205–215, 1988

    Google Scholar 

  74. Cloninger CR, Rice J, Reich T: Multifactorial inheritance with cultural transmission and assortative mating. II. A general model of combined polygenic and cultural inheritance. Am J Hum Genet 31: 176–198, 1979

    Google Scholar 

  75. Bouchard C: Genetic and environmental influences on regional fat distribution. In: Y Oomura et al. (eds.) Progress in obesity research 1990. John Libbey & Co Ltd, 1991,pp 303–308

  76. Bouchard C, Tremblay A, Després JP et al.: The response to long-term overfeeding in identical twins. N Engl J Med 322: 1477–1482, 1990

    Google Scholar 

  77. Poehlman ET, Tremblay A, Nadeau A, Dussault J, Thériault G, Bouchard C: Heredity and changes in hormones and metabolic rates with short-term training. Am J Physiol (Endocrinol Metab) 250: E711-E717, 1986

    Google Scholar 

  78. Després JP, Moorjani S, Tremblay A et al.: Heredity and changes in plasma lipids and lipoproteins after short-term exercise training in men. Arteriosclerosis 8: 402–409, 1988

    Google Scholar 

  79. Tremblay A, Poehlman E, Nadeau A, Pérusse L, Bouchard C: Is the response of plasma glucose and insulin to short-term exercisetraining genetically determined? Horm Metab Res 19: 65–67, 1987

    Google Scholar 

  80. Bouchard C, Pérusse L, Leblanc C: Using MZ twins in experimental research to test for the presence of a genotype-environment interaction effect. Acta Genet Med Gemellol 39: 85–89, 1990

    Google Scholar 

  81. Pouliot MC, Després JP, Moorjani S et al.: Apolipoprotein E polymorphism alters the association between body fatness and plasma lipoproteins in women. J Lipid Res 31: 1023–1029, 1990

    Google Scholar 

  82. Davignon J, Gregg RE, Sing CF: Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 8: 1–21, 1988

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physical Activity Sciences Laboratory, Laval University, Canada

    Jean-Pierre Després, Angelo Tremblay & Claude Bouchard

  2. Lipid Research Center, Canada

    Sital Moorjani & Paul J. Lupien

  3. Diabetes Research Unit, Laval University Medical Research Center, Ste-Foy, Quebec, Canada

    André Nadeau

Authors
  1. Jean-Pierre Després
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sital Moorjani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul J. Lupien
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Angelo Tremblay
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. André Nadeau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claude Bouchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Després, JP., Moorjani, S., Lupien, P.J. et al. Genetic aspects of susceptibility to obesity and related dyslipidemias. Mol Cell Biochem 113, 151–169 (1992). https://doi.org/10.1007/BF00231535

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00231535

Key words

Search

Navigation