Maternal obesity and high-fat diet (HFD) consumption are known to impact the development of offspring and predispose them toward future obesity and insulin resistance, likely through a variety of mechanisms. One previously unexplored mechanism is the gastrointestinal enteroendocrine pathway, which plays a critical role in regulating gut motility and absorption, appetite, and glucose homeostasis.The current study sought to characterize enteroendocrine hormone expression patterns across the primate GI tract and evaluate the impact of early HFD exposure on the density of these cells.
Japanese macaque dams were fed either a control diet (CTR, 15% calories from fat) or a HFD (36% calories from fat) prior to and during pregnancy and lactation.Offspring were then weaned, at ~6-8 months of age, onto either CTR or HFD creating four diet groups: maternal and post-weaning CTR (mCTRpCTR), maternal CTR and post-weaning HFD (mCTRpHFD), maternal HFD and post-weaning CTR diet (mHFDpCTR) or maternal and post-weaning HFD (mHFDpHFD). The GI tract was dissected upon necropsy at 3 years of age, and examined by IHC and RNAscope.
As expected, serotonin (5HT) was present throughout the GI tract. Cholecystokinin (CCK) was limited to the upper portion of the small intestine, while peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) were mostly found in the ileum and colon.Quantification of 5HT cells showed no difference between treatment groups in the small intestine, but increased 5HT cells in the ascending colon with post-weaning HFD.No differences in CCK cell numbers were observed between the four treatment groups.
These results indicate that maternal diet alone has little impact on 5HT and CCK cell density, whereas 5HT is upregulated with postnatal HFD consumption and may act to increase motility and/or alter microbiome function.