l-Glutamine supplementation promotes an improved energetic balance in Walker-256 tumor–bearing rats

Abstract

We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor-bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed. Protein expression levels of key enzymes of gluconeogenesis, that is, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, were analyzed by western blot and immunohistochemical techniques. In addition, plasma corticosterone, glucose, insulin, and urea levels were evaluated. The WTG group showed significantly increased plasma glucose and insulin levels (p < 0.05); however, plasma corticosterone and urea remained unchanged. Moreover, the WTG group showed increased immunoreactive staining for jejunal phosphoenolpyruvate carboxykinase and increased expression of duodenal glucose-6-phosphatase. Furthermore, the WTG group presented with less intense cancer cachexia and slower tumor growth. These results could be attributed, at least partly, to increased intestinal gluconeogenesis and insulinemia, and better glycemia maintenance during fasting in Walker-256 tumor rats on a diet supplemented with l-glutamine.

Nutritional Interventions in Cancer Cachexia: Evidence and Perspectives From Experimental Models

“…Furthermore, L-glutamine supplementation was associated with a significant elevation of glucose and insulin levels compared to control. The resulting hyperglycemia is probably attributable to the increased activity of gluconeogenic enzymes in the small intestine due to the increased availability of glutamine as a glucose precursor (41). All together, these studies suggest a beneficial effect of glutamine on cancer cachexia via enhancing intestinal health and energy metabolism.…”

“…Supplementation with 2% L-glutamine showed to attenuate cancer-induced cachexia, indicated as preserved body weight loss and a lower cachexia index, in rats bearing the Walker 256 tumor (39)(40)(41)(42)(43). Furthermore, tumor growth was inhibited in tumor-bearing rats supplemented with L-glutamine (39)(40)(41)(42). In cachectic rats, Walker 256 tumor growth caused considerable changes in small intestine metabolism (44).…”

A Time-Course Comparison of Skeletal Muscle Metabolomic Alterations in Walker-256 Tumour-Bearing Rats at Different Stages of Life

“…In this context, analysis of the skeletal muscle metabolites could provide a direct clue for biomarker research and also be applied for early detection of this syndrome [ 20 ]. Most of the preclinical cancer studies evaluated the metabolic muscle changes in cachectic tumour-bearing rats aged 8–12 weeks, representing an adult host [ 21 , 22 , 23 ]. The definition of “adult” in this context is likely to be related to the sexual maturity of the rodent, which is not a sufficient basis for considering the total development of the animal.…”

Energy metabolism in cachexia

“…However, alterations in expression or localization of the major intestinal glucose (SGLT1, GLUT5, GLUT2) and lipid (CD36, NPC1L1, SRB1) transporters, as seen upon fasting and refeeding , are likely. Altered intestinal gluconeogenesis, a recently identified regulator of the central control of glucose and energy homeostasis, may further contribute to the energetic imbalance observed in cachexia: Tumor‐bearing rats show ameliorated wasting when fed an l‐glutamine‐rich diet, activating intestinal gluconeogenesis and thereby improving glycemia .…”