Increased glucose availability activates chicken thymocyte metabolism and survival.

Glucose metabolism in mammalian thymocytes is coupled to their development and selection in the thymus. In chickens, thymocytes develop in a low glucose concentration in ovo and a high glucose concentration posthatch. To determine the effect of glucose concentration on thymocyte glucose metabolism, embryonic thymic lobes were cultured in media containing varying glucose concentrations and thymocytes were isolated for analysis. Glucose transporter-1 (Glut-1) and Glut-3 mRNA abundance was at least 2-fold higher in thymocytes incubated with 10 and 20 mmol/L glucose than in those incubated with 0 mmol/L glucose (P < 0.05) and glucose uptake was greatest in thymocytes incubated with 20 mmol/L glucose (P < 0.05). Thymocytes incubated with 0 and 20 mmol/L glucose had 185% greater hexokinase activity than in those incubated with 10 mmol/L glucose (P < 0.05). Consequently, thymocyte glucose utilization was dependent upon glucose availability. Increased glucose utilization resulted in a higher mitochondrial membrane potential in thymocytes incubated with 15 mmol/L glucose than in those incubated with 5 mmol/L glucose (P < 0.05), indicating enhanced thymocyte energy status in response to high glucose concentrations. Additionally, thymocyte viability was lower in thymocytes incubated with 5 mmol/L glucose than in those incubated with 10 and 15 mmol/L glucose (P < 0.05) and rates of thymocyte apoptosis were higher in thymocytes incubated with 5 mmol/L glucose than in those incubated with 15 mmol/L glucose (P < 0.05). Glucose availability induced metabolic changes in thymocytes that altered their energy status and survival. Consequently, these data indicate that glucose availability may influence the development of naïve T cells in the chicken thymus.

Energy metabolism in developing chicken lymphocytes is altered during the embryonic to posthatch transition.

Adequate energy status in lymphocytes is vital for their development. The ability of developing chicken lymphocytes to acquire and metabolize energy substrates was determined during embryonic days (e) and neonatal days (d) of life when primary-energy substrate metabolism is altered at the whole-animal level. In 3 experiments, bursacytes and thymocytes were isolated on e17, e20, d1, d3, d7, or d14 to analyze markers associated with glucose, glutamine, and lipid metabolism. Bursacyte glucose transporter-3 (Glut-3) mRNA abundance increased from d1 to d14 and hexokinase-1 (HK-1) mRNA abundance was maximum on e20 (P<0.05). Thymocyte Glut-1, Glut-3, and HK-1 mRNA abundance increased from e17 to d14 (P<0.05). HK enzyme activity increased from e20 to d3 in bursacytes and d3 to d7 in thymocytes (P<0.05). Glucose uptake by bursacytes and thymocytes was greater on d14 compared to d1 and d7 (P<0.05). Bursacyte and thymocyte sodium coupled neutral amino acid transporter-2 and glutaminase (GA) mRNA abundance increased from e20 to d7 (P<0.05). GA enzyme activity increased from e20 to d7 in bursacytes (P<0.05) and did not change in thymocytes. Carnitine palmitoyl transferase enzyme activity did not change over time in either cell type. These studies suggest that developing B and T lymphocytes adapt their metabolism during the first 2 wk after hatch. Developing lymphocytes increase glucose metabolism with no change in fatty acid metabolism and bursacytes, but not thymocytes, increase glutamine metabolism. Understanding the factors that regulate lymphocyte development in neonatal chicks may help promote their adaptive immune responses to pathogens in early life.