Dietary DHA and ARA alter the expression of 1700 hepatic genes including the tumor suppressor TOB1 in baboon neonates

Abstract

Background. We have recently shown that 1100 cerebral genes are differentially expressed in 12 week old baboon neonates consuming medium and high levels of DHA, with ARA. Here we report on differential hepatic gene expression induced by these diets.Methods. Baboon neonates were randomized at birth to three formulas: C, 0/0 DHA/ARA; L, 0.33/0.67%w/w; L3, 1.0/0.67. At 12 weeks, liver was collected and Affymetrix Gene chips assessed gene expression. Significance was determined by t‐tests, and Ingenuity® pathway analysis detected gene relationships.Results. More than 1700 of 54,000 probe sets (ps) were differentially expressed. Most significantly upregulated was TOB1, hepatic tumor suppressor associated with ERBB2. SCD (9‐desaturase) and FADS1 (5‐desaturase) were downregulated. ELOVL6, a PUFA elongase and BHMT (one carbon metabolism) were upregulated with increasing DHA. Ingenuity pathway analysis identified network TOB1 and SCD with many genes interacting with CTNNB1 and ERBB2. A number of (n = 52) transcripts with predicted peroxisome proliferator response elements were differentially expressed, including TOB1.Conclusions. Dietary DHA/ARA within the normal range found in breastmilk had widespread influence on gene expression, including TOB1 and many genes associated with PUFA metabolism. Funding: Mead Johnson Nutritionals, Evansville, IN.