Peripheral serotonin accounts for ~98% of the body’s total serotonin and recent work has been focused on the importance of peripheral serotonin on metabolic functions ( 3). Tph2 is predominantly expressed in the central nervous system and Tph1 is expressed in the peripheral nervous system ( 28). Tryptophan is catalyzed to 5-hydroxy- l-tryptophan by the rate limiting enzyme tryptophan hydroxylase 1 and 2 ( Tph1 and Tph2, respectively) and is then converted to serotonin by aromatic amino acid decarboxylase ( 28). Serotonin is formed from the amino acid tryptophan. Further research is required to completely understand the physiological significance of our results on peak lactation mammary physiology and the contribution of serotonin. However, 3,529 DEGs were observed between WT-HFD and Tph1-KO-HFD mice, including cell cycle regulation and MAPK pathways being significantly enriched. We did not observe many differentially expressed genes in WT and Tph1-KO dams fed LFD.
Genes were further filtered by mean normalized read count with a cutoff 310. Differentially expressed genes (DEGs) were first filtered by adjusted P value (cutoff ≤ 0.05) and fold-change (FC, cutoff ≥2). Dams were euthanized on lactation day 11. WT and Tph1-KO female mice were assigned to either an LFD or HFD beginning at 3 wk of age ( n = 4/group). 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. Little is known about the function of Tph1 and how peripheral serotonin affects mammary gland function during pregnancy and lactation. Peripheral serotonin inhibition has been associated with resistance to obesity in male mice fed an 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). 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).
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