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.
Highlights
Obesity has become a significant public health problem worldwide, and it is associated with various comorbidities [1,2,3,4,5]
By using the glucose clamp with tracer infusion, we investigated whole body insulin sensitivity associated with the effect of insulin on hepatic glucose production and glucose uptake in muscle and adipose tissue
These beneficial effects seem to be associated with tissue-specific insulin resistance in adipose tissue, which prevents the increase in adipose mass in these mice
Summary
Obesity has become a significant public health problem worldwide, and it is associated with various comorbidities [1,2,3,4,5]. Human and rodents studies demonstrated that, under a positive energy balance, the white adipose tissue triggers an immune response, which develops low-grade inflammation milieu, associated with infiltration of immune cells [7,8,9]. Many efforts have been made to prevent and treat obesity and to reduce the low-grade inflammatory status, including hypocaloric diets combined or not combined with physical activity and drugs in humans [13]. The complexity and time spent in this treatment often lead to weight recovery [14]. It will be useful if an obesity treatment strategy takes into account single nutrient supplementation. Studies that evaluated the potential of oral glutamine supplementation decreasing body weight and fat mass in an obese human being are scarce [21,22,23]
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