Oral Glutamine Supplementation Reduces Obesity, Pro-Inflammatory Markers, and Improves Insulin Sensitivity in DIO Wistar Rats and Reduces Waist Circumference in Overweight and Obese Humans.

In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.

Oral supplementation with L-glutamine alters gut microbiota of obese and overweight adults: A pilot study.

OBJECTIVE: The aim of this study was to determine whether oral supplementation with L-glutamine (GLN) modifies the gut microbiota composition in overweight and obese adults. METHODS: Thirty-three overweight and obese adults, ages between 23 and 59 y and body mass index between 25.03 and 47.12 kg/m(2), were randomly assigned to receive either oral supplementation with 30 g of L-alanine (ALA group control) or 30 g of GLN (GLN group) daily for 14 d. We analyzed the gut microbiota composition with new-generation sequencing techniques and bioinformatics analysis. RESULTS: After 14 d of supplementation, adults in the GLN group exhibited statistically significant differences in the Firmicutes and Actinobacteria phyla compared with those in the ALA group. The ratio of Firmicutes to Bacteroidetes, a good biomarker for obesity, decreased in the GLN group from 0.85 to 0.57, whereas it increased from 0.91 to 1.12 in the ALA group. At the genus level, Dialister, Dorea, Pseudobutyrivibrio, and Veillonella, belonging to the Firmicutes phylum, had statistically significant reduction. CONCLUSION: Oral supplementation with GLN, for a short time, altered the composition of the gut microbiota in overweight and obese humans reducing the Firmicutes to Bacteroidetes ratio, which resembled weight loss programs already seen in the literature.