Figure 1

Maternal high fat diet during gestation and lactation alters hepatic expression of key genes and miRNAs in the offspring. A maternal HF diet during gestation and lactation increased hepatic Igf2 expression in the offspring, which may be required for the up-regulation of ppar-α/cpt-1a by HF diet as suggested by our data presented in the Table 2. Increased ppar-α suppresses expression of let-7c, facilitates hepatic growth. Igf2 could down regulate let-7c through increased expression of ppar-α. Increased expression of ppar-α and reduced expression of miR-122 may increase hepatic fatty acid oxidation in the offspring. Igf1 receptor (Igf1R) and citrate synthase (CS) are predicted targets shared by both miR-122 and miR-494. Inhibition of Igf1R has been confirmed very recently [86]. Similar to miR-122, maternal HF offspring have reduced miR-494 levels, which favour increased Igf1R and CS activities. Several key proteins involved in epigenetics are predicted targets for miRNAs, in particular, methyl-CpG binding protein 2 are predicted targets for 5 miRNAs (miR-709, let-7s, miR-122, miR-194 and miR-26a) showing reduced levels in maternal HF fed offspring. Histone 4 H4 are predicted targets for 5 miRNAs (miR-503*, miR-770-3p, miR-369-3p, miR-197 and miR-667) showing increased levels in maternal HF fed offspring. Arrows suggest stimulatory and blocked arrows inhibitory effects. Solid lines represent established relationships whereas broken lines represent relationships not yet confirmed experimentally. FFA: free fatty acids. CS: citrate synthase, ppar-a: peroxisome proliferator activated receptor-alpha, cpt: carnitine pamitoyltransferase, MBD: methyl-CpG binding domain protein, MECP2:Methyl-CpG-binding protein 2, CHD4:chromodomain helicase DNA binding protein 4, DOT1L: DOT1-like, histone H3 methyltransferase, HIC2: hypermethylated in cancer 2, Hist4H4, histone 4 H4.