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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

1
School of Applied Sciences, State University of Campinas (UNICAMP), Limeira 13484-350 SP, Brazil
2
Department of Internal Medicine, State University of Campinas (UNICAMP), Campinas 13083-887 SP, Brazil
*
Author to whom correspondence should be addressed.
Equal contributors.
Nutrients 2019, 11(3), 536; https://doi.org/10.3390/nu11030536
Received: 1 February 2019 / Revised: 18 February 2019 / Accepted: 24 February 2019 / Published: 1 March 2019
(This article belongs to the Special Issue Energy Intake and Human Health)
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Abstract

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. View Full-Text
Keywords: obesity; glutamine supplementation; inflammation; insulin sensitivity; cytokines; clamp; LPS; hexosamine obesity; glutamine supplementation; inflammation; insulin sensitivity; cytokines; clamp; LPS; hexosamine
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Abboud, K.Y.; Reis, S.K.; Martelli, M.E.; Zordão, O.P.; Tannihão, F.; de Souza, A.Z.Z.; Assalin, H.B.; Guadagnini, D.; Rocha, G.Z.; Saad, M.J.A.; Prada, P.O. 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. Nutrients 2019, 11, 536.

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