Glutamsate Supplementation Regulates Tight Junction Protein Abundance and Amino Acid Transporters in the Jejunum of Low-Protein Diet-Fed Rats.

BACKGROUND

Glutamate has been demonstrated to promote intestinal development and enhance barrier integrity, suggesting its potential in alleviating intestinal dysfunction in weaned rats. Moreover, low-protein diets (LCP + Ala) impair intestinal barrier function by reducing tight junction (TJ) integrity and amino acid transport, which may be mitigated through glutamate supplementation.

OBJECTIVES

This study investigated the impacts of glutamate supplementation on TJ protein and amino acid transporter expression in the jejunum of LCP + Ala-fed rats.

METHODS

Weaned male Sprague-Dawley rats (21-d-old; n = 9/group) were divided into normal-protein diet group (18.1% crude protein [CP]), LCP + Ala group (14.5% CP), or LCP + Ala supplemented with 2.07% glutamate group (14.5% CP). After 18 d, average daily gain (ADG; mean values are presented), blood urea nitrogen (BUN), amino acid transport-related genes, intestinal morphology, and TJ protein abundance were assessed. Data were expressed as means ± standard error of the mean using 1-way analysis of variance with Duncan's test (P < 0.05).

RESULTS

Compared with control, protein restriction reduced ADG by 23.5% (6.64 ± 0.19 compared with 8.68 ± 0.20 g/d, P < 0.01); however, glutamate reversed ADG to control (7.57 ± 0.18 g/d, P < 0.01). Additionally, protein restriction increased BUN by 98.8% (3.86 ± 0.27 compared with 1.94 ± 0.15 mmol/L, P < 0.01), whereas glutamate normalized BUN (1.74 ± 0.16 mmol/L, P < 0.01). Protein restriction also decreased jejunal villus height by 30.9% (402 ± 25 compared with 581 ± 23 μm, P < 0.01), which was restored by glutamate (631 ± 34 μm, P < 0.01). Compared with control, protein restriction reduced the expression of excitatory amino acid transporter 3, occludin, claudin-1, and p62 (sequestosome 1). Glutamate restored their expression to 107%, 184%, 104%, and 104% of control, respectively, representing increases of 205%, 567%, 94%, and 105% compared to protein restriction (P < 0.01).

CONCLUSIONS

In weaned rats fed LCP + Ala, glutamate improved growth performance by enhancing jejunum morphology and TJ function, promoting amino acid transport, and modulating the general control nonderepressible 2/the α subunit of eukaryotic initiation factor 2/activating transcription factor 4/p62 signaling pathway.