Consequences of age-related splanchnic sequestration of leucine on interorgan glutamine metabolism in old rats

Abstract

Dietary leucine (Leu) serves as a nitrogen donor for de novo glutamine (Gln) synthesis in muscle. However, aging is characterized by an increase in the splanchnic extraction of Leu (SPELeu), i.e., splanchnic sequestration (SSLeu), which may affect muscle Gln metabolism and its subsequent homeostasis at the whole-body level. The aim of the work was to assess the effect of age-related SSLeu on Gln metabolism in the muscle, gut, liver, kidney, and Gln exchanges among these organs during fed conditions. Young-adult (3-mo-old) or aged (24-mo-old), male Sprague-Dawley rats were studied during fed condition [infusion of amino acids (AA) into the duodenum from time 0 min (T0) to T60] under anesthesia. L-[5-15N]Gln and L[1-13C]Leu were infused into the jugular vein and L-[5,5,5-2H3]Leu into the duodenum. At T60, blood samples were taken from carotid artery, portal vein, hepatic vein, renal vein, and inferior vena cava for tracer-tracee ratio and AA level measurements. SSLeu was observed in old rats and was negatively correlated with muscle Gln production ( r = −0.501, P < 0.01). In addition, reduced Gln muscle release in old rats was accompanied by reduced Gln uptake by the gut and kidney. However, net Gln balance across organs was not different between young adult and old rats. During fed conditions in old rats, muscle Gln production and release are reduced in relation to the observed, increased SPELeu and reduced renal and intestinal Gln uptake to maintain whole-body Gln homeostasis. Our results demonstrate the existence of an age-related change of interorgan Gln metabolism, which may be, in part, driven by SSLeu.