# L-Theanine Ameliorates Metabolic Dysregulation and Adverse Fetal Outcomes in a Mice Model of Gestational Obesity: Association with FXR/FGF15 Signaling

## TL;DR

L-theanine improves pregnancy outcomes in obese mice by reducing metabolic issues and inflammation, possibly through the FXR/FGF15 pathway.

## Contribution

Demonstrates L-theanine's potential to mitigate gestational obesity effects via gut microbiota and FXR/FGF15 signaling.

## Key findings

- L-theanine reduced weight gain, adiposity, and metabolic markers in gestational obesity mice.
- L-theanine suppressed inflammation and improved gut barrier function in the mice model.
- L-theanine mitigated placental abnormalities and improved neonatal weight outcomes.

## Abstract

In this study, we investigated whether L-theanine (LTA) ameliorates adverse pregnancy outcomes in high-fat diet (HFD)-induced gestational obesity mice. Gestational obese mice models received HFD and fecal microbiota transplantation (FMT) from pregnant obese women, followed by LTA treatment. Gut microbiota DNA from six obese and six normal pregnant women was analyzed. Also assessed were lipid profiles, inflammatory factors, gut permeability, FXR/FGF15 expression, pup weight, and placental function. Alpha- and beta-diversity analyses showed reduced gut microbial diversity in the obese pregnant women. Postpartum hemorrhage, cholesterol, and triglycerides inversely correlated with Weissella, while BMI was positively associated with Escherichia-Shigella. Neonatal weight correlated positively with Subdoligranulum and negatively with Megamonas. Fasting glucose was significantly positively associated with Bacteroides vulgatus, whereas neonatal body weight inversely correlated with Eubacterium ramulus. In gestational obesity mice, LTA administration reduced weight gain, visceral/gonadal adiposity, metabolic markers (fasting glucose/insulin/cholesterol), gut barrier dysfunction (TNF-α, IL-6, IL-8, Claudin-2), and linked to FXR/FGF15 pathway alterations. Furthermore, LTA intervention suppressed MCP-1, IL-1β, F4/80 and hepatic lipid metabolism regulators (CD36, SREBP1c, SCD1, GLUT4, Cyp7a1, IRS-1), while also mitigating placental tissue junction zone abnormalities and pup weight. To sum up, LTA-mediated attenuation of adverse pregnancy outcomes associates with FXR/FGF15 pathway alterations, concomitant with restoration of metabolic homeostasis and inflammation suppression.