Differential regulation of hepatic transcription factors in the wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids

Abstract

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 B12) 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 B12 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 280uC. 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 PPARa and PPARc expression was lower (p,0.05) in the BD group although there were no differences in the expression of SREBP-1c, LXRa and RXRa expression. Omega-3 fatty acids supplementation to this group normalized (p,0.05) levels of both PPARa and PPARc but reduced (p,0.05) SREBP-1c, LXRa and RXRa 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) PPARa, SREBP-1c and RXRa 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. © 2014 Meher et al.