Differential Regulation of Hepatic Transcription Factors in the Wistar Rat Offspring Born to Dams Fed Folic Acid, Vitamin B-12 Deficient Diets and Supplemented with Omega-3 Fatty Acids

作者：Meher Akshaya; Joshi Asmita; Joshi Sadhana^*

来源：PLos One, 2014, 9(2): e90209.

DOI：10.1371/journal.pone.0090209

Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B-12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B-12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80 degrees C. Maternal micronutrients deficiency resulted in lower (p<0.05) levels of pup liver docosahexaenoic acid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPAR alpha and PPAR gamma expression was lower (p<0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXR alpha and RXR alpha expression. Omega-3 fatty acids supplementation to this group normalized (p<0.05) levels of both PPAR alpha and PPAR gamma but reduced (p<0.05) SREBP-1 gamma, LXR alpha and RXR alpha expression. There was no change in any of the transcription factors in the pup liver in the FD group. Omega-3 fatty acids supplementation to this group reduced (p<0.05) PPAR alpha, SREBP-1 gamma and RXR alpha expression. Pup liver global methylation levels were higher (p<0.01) in both the micronutrients deficient groups and could be normalized (p<0.05) by omega-3 fatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring.

• 出版日期2014-2-28