Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity
Abstract
Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.
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BibTeX
@article{lefebvre2026opposite,
title = {{Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity}},
author = {Candice Lefebvre and Adam Tiffay and Charles-Edward Breemeersch and Virginie Dreux and Christine Bôle-Feysot and Charlène Guérin and Jonathan Breton and Elise Maximin and Magali Monnoye and Pierre Déchelotte and Véronique Douard and Moïse Coëffier and Alexis Goichon},
journal = {Food Research International},
year = {2026},
month = sep,
doi = {10.1016/j.foodres.2026.120038},
url = {https://normandie-univ.hal.science/hal-05750824v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity
AU - Candice Lefebvre
AU - Adam Tiffay
AU - Charles-Edward Breemeersch
AU - Virginie Dreux
AU - Christine Bôle-Feysot
AU - Charlène Guérin
AU - Jonathan Breton
AU - Elise Maximin
AU - Magali Monnoye
AU - Pierre Déchelotte
AU - Véronique Douard
AU - Moïse Coëffier
AU - Alexis Goichon
PY - 2026
DA - 2026/09/15
JO - Food Research International
DO - 10.1016/j.foodres.2026.120038
UR - https://normandie-univ.hal.science/hal-05750824v1
AB - Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.
SN - 0963-9969
ER -