Article thumbnail

Genetic variation in lipid desaturases and its impact on the development of human disease

By Diana M Merino, David WL Ma and David M Mutch


Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management

Topics: Review
Publisher: BioMed Central
OAI identifier:
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles


  1. (2010). A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1. J Lipid Res
  2. (2009). A: Does genetic variation in the {Delta}6-desaturase promoter modify the association between {alpha}-linolenic acid and the prevalence of metabolic syndrome?
  3. (2001). Activity of human 5 and 6 desaturases on multiple n-3 and n-6 polyunsaturated fatty acids. FEBS letters
  4. (2010). al: A genome-wide perspective of genetic variation in human metabolism. Nat Genet
  5. (2009). al: Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol
  6. (2004). Alteration of polyunsaturated fatty acid status and metabolism in health and disease. Reprod Nutr Dev
  7. (2004). Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.
  8. (2002). Attie AD: Loss of stearoyl-CoA desaturase1 function protects mice against adiposity. Proc Natl Acad Sci USA
  9. (2000). B: cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family. Genomics
  10. (2009). Biochemical and physiological function of stearoyl-CoA desaturase.
  11. (2009). Childhood obesity and cardiovascular disease. Paediatr Child Health
  12. (2006). Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum Mol Genet
  13. (2010). De Henauw S, et al: Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios.
  14. (2008). Dietary patterns and 15-y risks of major coronary events, diabetes, and mortality.
  15. (2009). DW: Experimental models and mechanisms underlying the protective effects of n-3 polyunsaturated fatty acids in Alzheimer’s disease.
  16. (2002). Efficiency of conversion of alpha-linolenic acid to long chain n-3 fatty acids in man. Curr Opin Clin Nutr Metab Care
  17. (2008). Epidemiology of diabetes and diabetes-related complications. Phys Ther
  18. (2008). et al: Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol
  19. (2005). et al: Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab
  20. (2009). et al: Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet
  21. (2002). et al: Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia.
  22. (2004). et al: Triglyceride levels are ethnicspecifically associated with an index of stearoyl-CoA desaturase activity and n-3 PUFA levels in Asians.
  23. (2009). Evidence for an association between genetic variants of the fatty acid desaturase 1 fatty acid desaturase 2 (FADS1 FADS2) gene cluster and the fatty acid composition of erythrocyte membranes.
  24. (2008). FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease.
  25. (2009). Fatty acids and cardiovascular disease. Nutr Rev
  26. (2004). function, and dietary regulation of delta6, delta5, and delta9 desaturases. Annu Rev Nutr
  27. (2008). Genes mirror geography within Europe. Nature
  28. (2008). Genetic variants of the FADS1 FADS2 gene cluster are associated with altered (n-6) and (n-3) essential fatty acids in plasma and erythrocyte phospholipids in women during pregnancy and in breast milk during lactation.
  29. (2006). Giugliano D: Diet and inflammation: a link to metabolic and cardiovascular diseases. Eur Heart J
  30. (2008). Giugliano D: Mediterranean dietary patterns and chronic diseases.
  31. (2007). H: {alpha}-Linolenic acid,{Delta} 6-desaturase gene polymorphism, and the risk of nonfatal myocardial infarction.
  32. (2004). Hayes KC: Dietary n-6 and n-3 fatty acid balance and cardiovascular health. Annu Rev Nutr
  33. (2010). HC: Variation in human erythrocyte membrane unsaturated Fatty acids: correlation with cardiovascular disease. Arch Pathol Lab Med
  34. (2001). Hu FB: Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk.
  35. (1998). Identification and characterization of a novel delta6/delta5 fatty acid desaturase inhibitor as a potential anti-inflammatory agent. Biochem Pharmacol
  36. (2006). Identifying regulatory hubs in obesity with nutrigenomics. Curr Opin Endocrinol Diabetes Obes
  37. (2005). Igal RA: Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage-independent growth, and survival in human transformed cells.
  38. (2000). Ikemoto A: n-6/n-3 Ratio of dietary fatty acids rather than hypercholesterolemia as the major risk factor for atherosclerosis and coronary heart disease.
  39. (2010). Impact of lifestyle on overall cancer risk among Japanese: The Japan public health center-based prospective study (JPHC Study).
  40. (2007). Lipid mediators in membrane rafts are important determinants of human health and disease. Appl Physiol Nutr Metab
  41. (2007). Moffitt TE: Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci USA
  42. (2009). Novel fatty acid desaturase 3 (FADS3) transcripts generated by alternative splicing. Gene
  43. (2007). Ntambi JM: Hepatic stearoyl-CoA desaturase-1 deficiency protects mice from carbohydrate-induced adiposity and hepatic steatosis. Cell Metab
  44. (2008). Ntambi JM: Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr Opin Lipidol
  45. (2009). Ntambi JM: Stearoyl-CoA desaturase and its relation to highcarbohydrate diets and obesity. Biochim Biophys Acta
  46. (2009). Ntambi JM: Stearoyl-CoA desaturase-1 deficiency attenuates obesity and insulin resistance in leptin-resistant obese mice. Biochem Biophys Res Commun
  47. (2009). Nutrigenetics: links between genetic background and response to Mediterranean-type diets. Public Health Nutr
  48. (2004). O’Rahilly S, et al: Analysis of the contribution to type 2 diabetes susceptibility of sequence variation in the gene encoding stearoyl-CoA desaturase, a key regulator of lipid and carbohydrate metabolism. Diabetologia
  49. (2005). Origins and evolution of the Western diet: health implications for the 21st century.
  50. (2008). P: SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids
  51. (2008). PC: Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examined. Clin Exp Allergy
  52. (2008). PC: Gender differences in the n-3 fatty acid content of tissues. Proc Nutr Soc
  53. (2001). Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans.
  54. (2006). Probing the role of stearoylCoA desaturase-1 in hepatic insulin resistance.
  55. (2007). Protective mechanisms of the Mediterranean diet in obesity and type 2 diabetes.
  56. (2010). Rafts and the battleships of defense: The multifaceted microdomains for positive and negative signals in immune cells. Immunol Lett
  57. (2003). Recent insights into stearoyl-CoA desaturase-1. Curr Opin Lipidol
  58. (2009). Riserus U: Associations between estimated fatty acid desaturase activities in serum lipids and adipose tissue in humans: links to obesity and insulin resistance. Lipids Health Dis
  59. (2007). Riserus U: Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity. Obesity (Silver Spring)
  60. (2009). Role of FADS1 and FADS2 polymorphisms in polyunsaturated fatty acid metabolism. Metabolism
  61. (2002). Selective inhibition of [Delta]-6 desaturase impedes intestinal tumorigenesis. Cancer Lett
  62. (2010). Simons K: Lipid rafts as a membrane-organizing principle. Science
  63. (2010). SR: The nutritional and clinical significance of lipid rafts. Curr Opin Clin Nutr Metab Care
  64. (2002). The importance of the ratio of omega-6/omega-3 essential fatty acids.
  65. (2010). Thijs C: FADS1 FADS2 gene variants modify the association between fish intake and the docosahexaenoic acid proportions in human milk.
  66. (2009). Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol
  67. (1990). WG: Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer’s disease. Neuroreport