Abstract
The cellular mechanisms underlying a greater risk of cardiometabolic disease in adult offspring exposed to maternal obesity are not known. Our prior work found reduced skeletal muscle mitochondrial metabolism and insulin sensitivity in offspring exposed to maternal (m) Western-style diet (WD), even when weaned onto a control diet (CD) in Japanese macaques. Here, we performed multiple comparisons of differentially expressed (DE) genes in skeletal muscle from lean juvenile offspring to test hypotheses specific to (1) the lasting effects of maternal diet composition and/or maternal adiposity on gene expression and (2) the transcriptional response to a chronic postweaning (pw)WD with and without prior exposure to mWD. Overall, we identified maternal (m)WD, and not maternal adiposity, as a principal driver of DE in offspring muscle even years after exposure with few differences observed in patterns of DE between offspring of lean vs. obese mWD dams. Transcriptional response to the pwWD was robust in mCD offspring but blunted by mWD, particularly in males, suggesting a potential priming of gene expression. KEGG enrichment analysis and assessment of top DE genes identified changes in key pathways associated with dysregulated metabolism and RNA processing. We conclude that mWD has a significant and lasting impact on offspring gene expression which likely contributes to observed skeletal muscle insulin resistance and metabolic dysregulation in these offspring.