Maternal obesity during pregnancy and suckling can programme a metabolic-like syndrome in offspring. This study aimed to determine the effects of maternal consumption of a high fat, high sucrose diet per se (in the absence of maternal obesity) on the metabolic and transcriptional profiles of adult offspring.
Female Sprague Dawley rats were fed a high saturated fat, high sucrose diet (HFD, 23% lard, 20% sucrose w/w n=5) or normal fat diet (NFD, 6% soy oil, 10% sucrose w/w, n=6) for 3 weeks prior to mating, throughout gestation and suckling. At 21 days of age, all animals were weaned to the NFD and fed ad libitum. Adult offspring (12 months of age) of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation Sequencing was used to identify differentially expressed genes in the skeletal muscle (soleus) of the offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), inflammatory response (P<0.024), cytokine-cytokine receptor interaction (P<0.037). A further 8 pathways significantly enriched with down-regulated genes included oxidative phosphorylation (P<0.004), mitochondrial matrix (P<0.006) and electron transport/uncoupling (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complex II (P<0.05) and complex V expression (P<0.05).
On a normal diet, offspring of non-obese HFD dams did not become obese adults, but developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data emphasize the importance of a balanced diet during pregnancy and lactation (even in the absence of obesity) to prevent the long-term consequences of fetal programming.