Abstract
Plasma levels of several amino acids are correlated with metabolic dysregulation in obesity and type 2 diabetes. To increase our understanding of human amino-acid metabolism, we aimed to determine splanchnic interorgan amino-acid handling. Twenty patients planned to undergo a pylorus preserving pancreatico-duodenectomy were included in this study. Blood was sampled from the portal vein, hepatic vein, superior mesenteric vein, inferior mesenteric vein, splenic vein, renal vein, and the radial artery during surgery. The difference between arterial and venous concentrations of 21 amino acids was determined using liquid chromatography as a measure of amino-acid metabolism across a given organ. Whereas glutamine was significantly taken up by the small intestine (121.0 ± 23.8 µmol/L; P < 0.0001), citrulline was released (−36.1 ± 4.6 µmol/L; P < 0.0001). This, however, was not seen for the colon. Interestingly, the liver showed a small, but a significant uptake of citrulline from the circulation (4.8 ± 1.6 µmol/L; P = 0.0138) next to many other amino acids. The kidneys showed a marked release of serine and alanine into the circulation (−58.0 ± 4.4 µmol/L and −61.8 ± 5.2 µmol/L, P < 0.0001), and a smaller, but statistically significant release of tyrosine (−12.0 ± 1.3 µmol/L, P < 0.0001). The spleen only released taurine (−9.6 ± 3.3 µmol/L; P = 0.0078). Simultaneous blood sampling in different veins provides unique qualitative and quantitative information on integrative amino-acid physiology, and reveals that the well-known intestinal glutamine–citrulline pathway appears to be functional in the small intestine but not in the colon.
Highlights
Gut microbiota are increasingly implicated in the pathogenesis of obesity and type 2 diabetes
Considering the association between plasma levels of certain amino acids and metabolic dysregulation in obesity and type 2 diabetes (McCormack et al 2013; Newgard 2012; Newgard et al 2009), detailed knowledge on human splanchnic aminoacid metabolism is critical to understanding overall metabolic regulation
Permission for the study was granted by the local Medical Ethics Committee of Maastricht University Medical Center (MEC 11-3-084) and the study was conducted according to the ethical standards of the Helsinki Declaration of 1975 and in accordance with the Medical Research Involving Human Subjects Act (WMO)
Summary
Gut microbiota are increasingly implicated in the pathogenesis of obesity and type 2 diabetes. The functional output of the gut microbiota, in particular short-chain fatty acids and amino acids, seems to affect metabolic homeostasis profoundly (Neis et al 2015; Wang et al 2011). Several amino acids released by gut bacteria can serve as precursors for the synthesis of short-chain fatty acids (Barker 1981) which, in turn, appear to contribute to body weight gain (Schwiertz et al 2010). Considering the association between plasma levels of certain amino acids and metabolic dysregulation in obesity and type 2 diabetes (McCormack et al 2013; Newgard 2012; Newgard et al 2009), detailed knowledge on human splanchnic aminoacid metabolism is critical to understanding overall metabolic regulation
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