Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

Samantha R Weaver,Allan S Prichard,Justin C Bohrer,Mark E Cook,Paola K Perez,Liana J Streckenbach,Jake M Olson,Laura L Hernandez,Christopher Torrens

doi:10.1371/journal.pone.0162432

Abstract

Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

Highlights

Breastfeeding provides significant health benefits to both infant and mother
The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet
Dam weight and pup mortality are elevated in WT high fat diet (HFD) relative to Tph1-/HFD mice

Summary

Introduction

Breastfeeding provides significant health benefits to both infant and mother. Longer durations of breastfeeding have been associated with reduced cholesterol and blood pressure, along withPLOS ONE | DOI:10.1371/journal.pone.0162432 September 7, 2016Serotonin Deficiency Improves Lactation in Mice reduced incidence of type 2 diabetes in the mother. Longer durations of breastfeeding have been associated with reduced cholesterol and blood pressure, along with. Breastfed infants have been demonstrated to show improved cognitive development, are likely protected against immune-related diseases, and have a reduced risk of obesity [1,2]. Difficulties with breastfeeding during the first week postpartum are associated with a greater risk of early termination of breastfeeding, as well as a lower chance of breastfeeding subsequent children [4]. There is a well-established relationship between maternal body mass index and DOL, with overweight and obese women more likely to experience DOL and terminate breastfeeding early [4,5,6,7]. It has been shown that women who were overweight or obese had lower prolactin response to suckling than normal-weight women at 48 hours and 7 days post-partum, local mammary gland dynamics in response to obesity have yet to be explored [12]

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