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Transcriptomic analysis investigating the interaction between peripheral serotonin and high fat diet feeding on mammary gene expression in mid-lactation mice.

Research paper by Adrienne A AA Cheng, Wenli W Li, Laura L LL Hernandez

Indexed on: 11 Dec '19Published on: 10 Dec '19Published in: Physiological genomics



Abstract

In order to understand the role of peripheral serotonin and its interaction with diet in mid-lactation mammary gene expression, our study uses tryptophan hydroxylase 1 knockout (-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 wildtype (WT) mice compared to dams fed a LFD. Peripheral serotonin inhibition has been associated with resistance to obesity in male mice fed a HFD. Little is known about the function of and how peripheral serotonin affects mammary gland function during pregnancy and lactation. In this study, WT and -KO models were used to investigate global transcriptomic changes in peak lactation mammary glands when dams were fed either a HFD or LFD (low-fat diet). WT and -KO female mice were assigned to either a LFD or HFD beginning at three weeks of age (n=4/group). Dams were euthanized on lactation day 11. Differentially expressed genes (DEGs) were first filtered by adjusted value (cutoff £ 0.05) and fold-change (FC, cutoff ³2). Genes were further filtered by mean normalized read count with a cutoff³10. We did not observe many differentially expressed genes in WT and -KO dams fed LFD. However, 3529 DEGs were observed between WT-HFD and -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.