# Exploring the contribution of mammary-derived serotonin on liver and pancreas metabolism during lactation

## TL;DR

This study explores how serotonin produced in the mammary gland affects liver and pancreas metabolism in mice during lactation.

## Contribution

The study reveals a novel role for mammary-derived serotonin in regulating insulin homeostasis during lactation.

## Key findings

- Mammary-derived serotonin is reduced by 50% in Wap-Cre x TPH1FL/FL mice during lactation.
- Reduced serotonin in the pancreas correlates with lower insulin levels but normal glucose levels.
- Mammary glands with lower serotonin show increased milk protein gene expression and altered adipocyte structure.

## Abstract

During lactation, the murine mammary gland is responsible for a significant increase in circulating serotonin. However, the role of mammary-derived serotonin in energy homeostasis during lactation is unclear. To investigate this, we utilized C57/BL6J mice with a lactation and mammary-specific deletion of the gene coding for the rate-limiting enzyme in serotonin synthesis (TPH1, Wap-Cre x TPH1FL/FL) to understand the metabolic contributions of mammary-derived serotonin during lactation. Circulating serotonin was reduced by approximately 50% throughout lactation in Wap-Cre x TPH1FL/FL mice compared to wild-type mice (TPH1FL/FL), with mammary gland and liver serotonin content reduced on L21. The Wap-Cre x TPH1FL/FL mice had less serotonin and insulin immunostaining in the pancreatic islets on L21, resulting in reduced circulating insulin but no changes in glucose. The mammary glands of Wap-Cre x TPH1FL/FL mice had larger mammary alveolar areas, with fewer and smaller intra-lobular adipocytes, and increased expression of milk protein genes (e.g., WAP, CSN2, LALBA) compared to TPH1FL/FL mice. No changes in feed intake, body composition, or estimated milk yield were observed between groups. Taken together, mammary-derived serotonin appears to contribute to the pancreas-mammary cross-talk during lactation with potential implications in the regulation of insulin homeostasis.