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
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
复制标题
DOI：
10.3390/nu11030536
复制
发表时间：
2019-03-01
期刊：
影响因子：
5.9
通讯作者：
Prada, Patricia Oliveira
中科院分区：
文献类型：
--
作者：
Abboud, Kahlile Youssef;Reis, Sabrina Karen;Prada, Patricia Oliveira
在本研究中，我们旨在研究慢性口服谷氨酰胺（Gln）补充剂是否会改变超重和肥胖人群的代谢参数和炎症特征，以及Gln是否会调节与胰岛素作用相关的大鼠关键组织中的分子通路。39名超重/肥胖志愿者连续14天服用30克谷氨酰胺或丙氨酸（ala对照）。评估体重（BW）、腰围（WC）、激素和促炎标志物。为了研究其分子机制，我们给高脂饮食（HFD）的Wistar大鼠注射Gln或Ala，并对其代谢参数、正糖高胰岛素钳夹和示踪剂进行检测。谷氨酰胺降低了超重志愿者的WC和血清脂多糖（LPS）。在肥胖组，Gln降低WC和血清胰岛素。WC的减少与LPS呈正相关。在HFD大鼠中，Gln减少了肥胖，改善了胰岛素的作用和信号传导，并逆转了肝脏和肌肉中葡萄糖代谢的缺陷。补充谷氨酰胺增加了肌肉葡萄糖摄取，逆转了肝脏葡萄糖产生的增加，同时减少了脂肪组织的葡萄糖摄取。AT的胰岛素抵抗伴随着该组织中IRS1 O-linked-glycosamine关联的增强，但在肝脏和肌肉中没有。这些数据表明，补充Gln通过己糖胺途径导致脂肪组织的胰岛素抵抗，并减少脂肪量，这与全身胰岛素作用的改善有关。因此，在将谷氨酰胺补充剂作为一种对超重和肥胖个体有益的治疗方法开处方之前，应该对人类进行更长时间的进一步研究。
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.