Biology subjects

Tiffay, A.

Publications and source records attributed to Tiffay, A..

4 recordsLinked to original sources

bioRxiv2026

Stress limits the beneficial effects of glutamine in male ob/ob mice

IntroductionObesity is a major health issue associated with metabolic and psychological comorbidities, as well as an increased prevalence of disorders of gut-brain interaction (DGBI). Obesity and DGBI share common mechanisms such as inflammation, gut barrier dysfunction, and alterations of gut microbiota, which are all known to be regulated by stress. Glutamine (Gln), which is essential to maintain intestinal integrity and immune response, may counteract these alterations. This study aimed to evaluate the effects of oral Gln supplementation on stress-induced response in obese mice. MethodsSeven-week-old male leptin-deficient ob/ob mice were assigned to four groups: control, chronic restraint stress (CRS), Gln-supplemented, or both CRS and Gln-supplemented. Gln was administered in drinking water for two weeks, and CRS was performed during the final 4 days. Metabolic parameters, intestinal permeability, inflammatory markers, gene and protein expression, and gut microbiota composition were assessed. ResultsStress increased plasma corticosterone levels but had a limited effect on metabolic parameters. In obese mice without stress, Gln supplementation reduced body weight gain, improved body composition and reduced inflammation in the visceral adipose tissue. These effects were lost under stress conditions, with an increase in fasting glycaemia. Stress reduced occludin protein levels, while Gln exerted context-dependent effects, decreasing gene expression of Tjp3, Cldn15 and Ccl2 in unstressed mice but increasing gene expression of multiple tight junction (Tjp2, Tjp3, Cldn12, Cgn, F11r, Marveld2) and inflammatory markers (Tlr2, Myd88, Irf3) under stress. Interestingly, in unstressed obese mice, Gln altered the composition of the gut microbiota, with changes in key bacterial taxa (Thermodesulfobacteriota and Clostridiaceae). This was associated with decreased levels of cecal short-chain fatty acids and increased levels of branched-chain fatty acids. ConclusionIn conclusion, Gln improves metabolic and adipose inflammatory parameters in genetically obese mice. However, these benefits are no longer observed when mice are under stress conditions. Since, Gln has been found to increase fasting glycaemia and colonic inflammation, in association with alterations of gut microbiota.

pathology↗

bioRxiv2026

Chronic Activity-Based Anorexia triggers a glial response in the hippocampus independent of intestinal epithelial Toll-Like Receptor 4

Anorexia nervosa is characterized by maladaptive eating behavior and cognitive dysfunction, which could be explained by a neuroinflammation. A gut dysbiosis could link gastrointestinal alterations to central dysfunctions, particularly via the toll-like receptor 4 (TLR4), which has been shown to play a key role in the activity-based anorexia (ABA) model. We aimed to evaluate the neuroinflammation and its behavioral consequences in the ABA model, and to decipher the role of the microbiota-gut-brain axis, and more specifically of TLR4, in these alterations of the central nervous system. We show that chronic restriction is more strongly associated with gut inflammation, cecal microbiota alteration and neuroinflammatory processes in the hippocampus than acute restriction. The hippocampal glial response is characterized by a loss of astrocyte density, and an increased number of deramified microglia. We further demonstrate that these alterations are independent of TLR4 expressed by intestinal epithelial cells. In conclusion, our results highlight that the chronicity of ABA-associated undernutrition alters the response of glial cells in the hippocampus that is linked with changes in microbiota composition, highlighting the importance of faster diagnosis and treatment of AN.

neuroscience↗

bioRxiv2025

Glutamine alters the response to stress in mice with diet-induced obesity in a sex-dependent manner.

RationalePatients with class III obesity often suffer from irritable bowel syndrome (IBS) while obesity and IBS share common pathophysiological mechanisms such as altered intestinal barrier function and gut microbiota dysbiosis. Oral glutamine (Gln) supplementation previously showed beneficial effects on gut barrier function in a sex-dependent manner and reduced abdominal pain in IBS patients. Thus, we assessed the sex-dependent response to an oral Gln supplementation in mice with diet-induced obesity and subjected to a chronic restraint stress to mimic IBS. MethodsMale (M) and female (F) C57BL/6 mice received a high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14) and were subjected or not to a restraint stress (S) for the 4 last days. From W12, mice received or not Gln in drinking water (2g/kg/day; n=12/group). Plasma corticosterone, body composition, glucose tolerance (OGTT), intestinal permeability, inflammatory markers in colonic and white adipose tissues, cecal microbiota and short-chain fatty acid (SCFA) composition have been assessed. Within each sex, groups were compared by Kruskal-Wallis test or a 1-way ANOVA test. ResultsIn M-HFD mice, chronic restraint stress was associated with a better glucose tolerance (-15,46% AUC) and a reduced fasting glycemia that was not observed in F-HFD mice. Gln partially prevented body weight loss, reduced plasma resistin, plasma corticosterone and colonic permeability in female stressed obese mice. In male stressed obese mice, Gln limited lean mass loss, reduced colonic permeability and Ccl2 mRNA level in the subcutaneous adipose tissue. Chronic restraint stress and Gln modified cecal microbiota in both sexes but cecal SCFA composition only in male mice. In particular, stress induced an increased abundance of Pseudomonadota in male mice that was partially restored after Gln supplementation. In addition, cecal total SCFA were reduced in Gln-supplemented stressed HFD male mice compared to unstressed HFD mice. In female HFD mice, stress associated to Gln supplementation increased the abundance of Thermodesulfobacteriota and reduced colonic expression of Cxcr3 mRNA. ConclusionsChronic restraint stress has beneficial effects on glycemia control in male HFD mice without additive effects of Gln supplementation. By contrast, Gln reduces stress-induced corticosterone level and body weight loss only in females. These data, as well as the differential impact of Gln on intestinal permeability and gut microbiota according to the sex, deserves further investigations to decipher the underlying mechanisms.

pathology↗

bioRxiv2024

Sex-dependent effects of a glutamine supplementation on metabolic disorders, intestinal barrier function and gut microbiota in mice with diet-induced obesity.

RationaleObesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. Glutamine (Gln) supplementation previously showed beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize in mice the sex-dependent effects of a Gln supplementation during high fat diet induced obesity. MethodsMale and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). From W12, mice received or not Gln in drinking water (2g/kg/day; n=12/group). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota and inflammatory/endocrine adipose response have been assessed. Data were analyzed using t-test or Mann-Whitney test (HFD effect), and two-way ANOVA (HFD x Gln) followed by Bonferroni post-tests. ResultsIn both male and female mice, Gln supplementation failed to improve body weight and body composition. However, Gln reduced glucose intolerance in HFD males (AUC reduced by 14.57%, p<0.05) that was associated to a partial restoration of plasma resistin and insulin and to a trend for a limitation of adipose inflammatory response. In males, Gln did not affect gut microbiota composition and colonic response. To the opposite, in females fed HFD, Gln supplementation led to gut microbiota changes (increase of Bacteroidota and Pseudomonadota phyla; increase of Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (TNF, IL-1{beta}, TLR4, Myd88, Irf3) that were associated to increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. ConclusionsHigh fat diet mice exhibit sex-dependent response to glutamine supplementation with protective effects in males and harmful effects in females. The role of gut microbiota should be deeply deciphered in further investigations.

pathology↗