Transcriptomic analysis investigating the interaction between peripheral serotonin and high-fat diet feeding on...

To understand the role of peripheral serotonin and its interaction with diet in midlactation mammary gene expression, our study uses tryptophan hydroxylase 1 knockout (Tph1-KO) mice fed a high-fat diet (HFD). It has previously been demonstrated that HFD feeding increases inflammatory and immune pathways in peak lactation mammary glands of mice and increases pup mortality in wild-type (WT) mice compared with dams fed a low-fat diet (LFD). Peripheral serotonin inhibition has been associated with resistance to obesity in male mice fed an HFD. Little is known about the function of Tph1 and how peripheral serotonin affects mammary gland function during pregnancy and lactation. In this study, WT and Tph1-KO models were used to investigate global transcriptomic changes in peak lactation mammary glands when dams were fed either an HFD or LFD. WT and Tph1-KO female mice were assigned to either an LFD or HFD beginning at 3 wk of age (n = 4/group). Dams were euthanized on lactation day 11. Differentially expressed genes (DEGs) were first filtered by adjusted P value (cutoff ≤ 0.05) and fold-change (FC, cutoff ≥2). Genes were further filtered by mean normalized read count with a cutoff ³10. We did not observe many differentially expressed genes in WT and Tph1-KO dams fed LFD. However, 3,529 DEGs were observed between WT-HFD and Tph1-KO-HFD mice, including cell cycle regulation and MAPK pathways being significantly enriched. Further research is required to completely understand the physiological significance of our results on peak lactation mammary physiology and the contribution of serotonin.