Exploring the Role of Fatty Acid on Transcription Factors Regulating Fatty Acid Metabolism with Emphasis on Trans Fatty Acid
- 1 Department of Cardiac Biochemistry, All India Institute of Medical Sciences, Delhi, India
- 2 Department of Surgery, All India Institute of Medical Sciences, Delhi, India
- 3 Department of Surgery, All India Institute of Medical Sciences, Delhi, India
- 4 Department of Surgery, All India Institute of Medical Sciences, Delhi, India
- 5 Centre of Chronic Disease Control, Delhi, India
- 6 Department of Cardiology, All India Institute of Medical Sciences, Delhi, India.
Abstract
Fatty acids are unique macromolecules as they act as biological modulators of transcription factors and regulate their own metabolism by controlling the activity or abundance of transcription factors of fatty acid metabolism either by RNA processing and RNA stability. Peroxisome Proliferator Activated Receptor (PPAR-γ) and Sterol Regulatory Element Binding Protein (SREBP-1c) are transcription factors expressed primarily in adipose tissue. We have studied the relation of fatty acid including trans fatty acid assessed in adipose tissue with the transcription factors. Adipose tissue was collected from 50 healthy subjects undergoing elective abdominal surgery. Fatty acid was assessed in the tissue by gas chromatography. The expressions of PPARγ and SREBP-1c were studied by real time RT-PCR. The expressions of PPARγ and SREBP1c were significantly correlated (r = 0.4 p < 0.005). The trans fatty acid did not show any significant correlation with expression but significant correlation was observed between DHA (Docosahexaenoic acid) and PPARγ expression (r = 0.33 p < 0.03) which remained significant (r = 0.87, p < 0.0001) after being adjusted for BMI and insulin. An upregulation of PPARγ led to decreased levels of SREBP1c. In conclusion, trans fatty acid did not affect the expressions of PPAR-γ and SREB1c in this study.
- D. B. Jump, “Dietary Polyunsaturated Fatty Acids and Regulation of Gene Transcription,” Current Opinion in Lipidology, Vol. 13, No. 2, 2002, pp. 155-164. doi:10.1097/00041433-200204000-00007
- G. Mann, “Metabolic Consequences of Dietrary Trans Fatty Acids,” Lancet, Vol. 343, No. 8908, 1994, pp. 1268-1271. doi:10.1016/S0140-6736(94)92157-1
- R. Micha and D. Mozaffarian, “Trans Fatty Acids: Effects on Metabolic Syndrome, Heart Disease and Diabetes,” Nature Reviews Endocrinology, Vol. 5, 2009, pp. 335-344. doi:10.1038/nrendo.2009.79
- T. T. Lu, J. J. Repa and D. J. Mangelsdorf, “Orphan Nu clear Receptors as eLiXiRs and FiXeRs of Sterol Me tabolism,” The Journal of Biological Chemistry, Vol. 276, 2001, pp. 37735-37738.
- J. M. Olefsky, “Nuclear Receptor Minireview Series,” The Journal of Biological Chemistry, Vol. 276, 2001, pp. 36863-36864. doi:10.1074/jbc.R100047200
- B. P. Kota, T. H. Huang and B. D. Roufogalis, “An Over view on Biological Mechanisms of PPARs,” Pharmacol ogical Research, Vol. 51, No. 2, 2005, pp. 85-94. doi:10.1016/j.phrs.2004.07.012
- P. Tontonoz, E. Hu and B. M. Spiegelman, “Stimulation of Adipogenesis in Fibroblasts by PPAR γ2, a Lipid-Ac tivated Transcription Factor,” Cell, Vol. 79, No. 7, 1994, pp. 1147-1156. doi:10.1016/0092-8674(94)90006-X
- X. Hua, J. Wu, J. L. Goldstein, M. S. Brown and H. H. Hobbs, “Structure of the Human Gene Encoding Sterol Regulatory Element Binding Protein-1(SREBPF1) and Localization of SREBPF1 and SREBPF2 to Chromosome 17p11.2 and 22q13,” Genomics, Vol. 25, No. 3, 1995, pp. 667-673. doi:10.1016/0888-7543(95)80009-B
- I. Shimomura, H. Shimano, J. D. Horton, J. L. Goldstein and M. S. Brown, “Differential Expression of Exons 1a 1nd 1c in mRNA for Sterol Regulatory Element Binding Protein-1 in Human and Mouse Organs and Cultured Cells,” Journal of Clinical Investigation, Vol. 99, No. 5, 1997, pp. 838-845. doi:10.1172/JCI119247
- J. Folch, M. Lees and G. H. S. Stanley, “A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues,” The Journal of Biological Chem istry, Vol. 226, 1957, pp. 497-509.
- A. Ascherio and W. C. Willett, “Metabolic and Athero genic Effects of Trans Fatty Acids,” Journal of Internal Medicine, Vol. 238 No. 2, 1995, pp. 93-96. doi:10.1111/j.1365-2796.1995.tb00906.x
- R. M. Machado, et al., “Intake of Trans Fatty Acids Causes Nonalcoholic Steatohepatitis and Reduces Adi pose Tissue Fat Content,” The Journal of Nutrition, Vol. 140, No. 6, 2010, pp. 1127-1132. doi:10.3945/jn.109.117937