A maternal high-fat, high-sucrose (HFS) diet alters offspring glucose and lipid homoeostasis through unknown mechanisms and may be modulated by folic acid. We investigated the effect of a maternal HFS diet on glucose homoeostasis, expression of genes and proteins associated with insulin signalling and lipid metabolism and the effect of prenatal folic acid supplementation (HFS/F) in male rat offspring. Pregnant Sprague-Dawley rats were randomly fed control (CON), HFS or HFS/F diets. Offspring were weaned on CON; at postnatal day 70, fasting plasma insulin and glucose and liver and skeletal muscle gene and protein expression were measured. Treatment effects were assessed by one-way ANOVA. Maternal HFS diet induced higher fasting glucose in offspring v. HFS/F (P=0·027) and down-regulation (P<0·05) of genes coding for v-Akt murine thymoma viral oncogene homolog 2, resistin and v-Raf-1 murine leukaemia viral oncogene homolog 1 (Raf1) in offspring skeletal muscle and acetyl-CoA carboxylase (Acaca), fatty acid synthase and phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit β in offspring liver. Skeletal muscle neuropeptide Y and hepatic Kruppel-like factor 10 were up-regulated in HFS v. CON offspring (P<0·05). Compared with CON, Acaca and Raf1 protein expression levels were significantly lower in HFS offspring. Maternal HFS induced higher homoeostasis model of assessment index of insulin resistance v. CON (P=0·030) and HFS/F was associated with higher insulin (P=0·016) and lower glucose (P=0·025). Maternal HFS diet alters offspring insulin sensitivity and de novo hepatic lipogenesis via altered gene and protein expression, which appears to be potentiated by folate supplementation.
Keywords: Acaca acetyl-CoA carboxylase; Akt2 V-Akt murine thymoma viral oncogene homolog 2; CON control; Ct threshold cycle; Fasn fatty acid synthase; HFS high-fat/high-sucrose; HFS/F folic-acid-supplemented; HOMA-IR homoeostasis model of assessment index of insulin resistance; IR insulin resistance; Klf10 Kruppel-like factor 10; PVDF polyvinylidenedifluoride; Pik3cb phosphatidylinositol-4; Raf1 V-Raf-1 murine leukaemia viral oncogene homolog 1; Slc2a4 solute carrier family 2; T2D type 2 diabetes; catalytic subunit β; facilitated GLUT; high-fat/high-sucrose; member 4; 5-bisphosphate 3-kinase; Fetal programming; Folic acid; High-fat high-sucrose diet; Insulin resistance; Lipid metabolism.