Maternal high fat diet exposure results in MyD88 dependent alteration in placental and offspring intestinal fatty acid transporters

Introduction: We know that offspring born to parents with obesity are more likely to be obese. We hypothesized that the maternal high fat diet (mHFD) exposure may increase placental and offspring small intestinal transport of fatty acids. We hypothesized both these processes would be dependent on the presence of MyD88. Methods: Wild-type (WT) and MyD88 deficient mice on either 60% mHFD or regular diet (RD) were profiled. The baseline expression of fatty acid transport proteins FATP1 and FATP4, fatty acid binding proteins FABP1, FABP4, and CD36 were profiled by qRT-PCR from placenta after C-section at E20, and offspring small intestine 2-weeks after birth. Serum from 0-day old RD and HFD WT mice were collected and analyzed using high-throughput, non-targeted mass spectroscopy based metabolic analysis. Results: In WT mice, we found FATP1 was increased 32-fold and FABP was increased 7-fold in the mHFD placenta. FATP2 was decreased 2-fold and FATP4 was decreased 2.5-fold in the mHFD offspring small intestine. In MyD88 KO mice, we found no difference in any of the above fatty acid transporters. Serum of neonatal pups showed unique clustering of metabolites by PCA analysis in HFD and RD mice, with increased butanoate and propanoate metabolites in mHFD offspring. Conclusion: Fatty acid transport regulators in the placenta and offspring small intestine were modified by exposure mHFD. In both the placenta and small intestine, this outcome was dependent on the presence of MyD88. Fatty acid metabolites were increased in the serum of neonatal pups exposed to mHFD. These findings suggest that mHFD exposure can modulate fetal metabolism and may be an opportunity for future development of therapeutics that target placental and intestinal transporters.