Short-chain fatty acid–supplemented total parenteral nutrition alters intestinal structure, glucose transporter 2 (GLUT2) mRNA and protein, and proglucagon mRNA abundance in normal rats

Abstract

Intestinal adaptation is a complex physiologic process that is not completely understood. Intravenous short-chain fatty acids (SCFAs) enhance intestinal adaptation after 80% enterectomy in rats. The purpose of this study was to examine rapid responses to SCFA-supplemented total parenteral nutrition (TPN) in the normal small intestine. After jugular catheterization, 31 Sprague-Dawley rats (weighing 258 +/- 3 g) were randomly assigned to receive standard TPN or an isoenergetic, isonitrogenous TPN solution supplemented with SCFAs (TPN+SCFA). Intestinal samples were obtained after 24 or 72 h of nutrient infusion. TPN+SCFA for 24 h increased (P < 0.05) the ileal RNA concentration (microg RNA/mg ileum) whereas TPN+SCFA for 72 h increased (P < 0.05) the ileal DNA concentration (microg DNA/mg ileum) and decreased (P < 0.05) the ileal protein concentration (microg protein/mg ileum). Ileal proglucagon mRNA abundance was elevated (P < 0.05) after 24 h of TPN+SCFA infusion and returned to levels seen with control TPN by 72 h. Glucose transporter 2 (GLUT2) mRNA was significantly higher (P < 0.05) in the TPN+SCFA groups at both time points when compared with control TPN groups. Ileal GLUT2 protein abundance in the 72-h TPN+SCFA group was significantly higher (P < 0.05) than that of all other groups. Sodium-glucose cotransporter (SGLT-1) mRNA and protein abundance and uptake of D-fructose and D-glucose did not differ between groups. Jejunal uptake of L-glucose and lauric acid was significantly higher (P < 0.05) after 72 h of TPN+SCFA than after 24 h, whereas the 24- and 72-h TPN groups did not differ. In summary, SCFAs led to rapid changes in ileal proglucagon and glucose transporter expression in rats receiving TPN and provide insights into therapeutic management of individuals with short bowel syndrome or intestinal malabsorption syndromes.

Gut microbiome and nonalcoholic fatty liver diseases

“…The beneficial effect is the improvement of the leaky gut (reduced permeability), which leads to lower plasma lipopolysaccharide (LPS) and cytokines levels, and consequently a decreased hepatic expression of oxidative stress and inflammatory markers. The knowledge gap here is that while the study of Cani et al is suggestive of a lower level of GLP-2 in ob/ob mice, this is not consistent with the reports that SCFAs are high in the gut of ob/ob mice (21) and SCFAs induce GLP-2 (28,30). Further studies on the interaction between SCFA and GLP-2 and the underlying mechanism may provide an explanation for this inconsistency.…”

“…The underlying mechanisms include the induction of nutrient transporters such as GLUT2 in enterocytes (27,28), the induction of enterocyte proliferation and the inhibition of apoptosis (29). Tappenden et al also noticed that SCFA supplementation induced the expression of ileal proglucagon mRNA and plasma glucagon-like peptide 2 (GLP-2), establishing the current hypothesis that the intestinotrophic effects of SCFAs are mediated by GLP-2 (28,30). Since SCFAs are elevated in the gut of obese patients, they may contribute to the development/ maintenance of obesity through elevated intestinal absorption.…”

Cloning of porcine proglucagon and effect of commensal bacteria on relative gene expression in the intestine of gnotobiotic pigs

“…The processed form of caspase-3 consists of two active subunits (17 and 12 kDa), which combine to form an active enzyme. Increased cellular abundance of the active subunits of caspase-3 is associated with increased apoptosis (Kothakota et al 1997;Thornberry and Lazebnik 1998). In the current study, active caspase-3 subunit abundance in the distal SI was highest in CV pigs, intermediate in EC pigs (detectable in exp.…”

Factors Enhancing Intestinal Adaptation after Bowel Compensation

“…Tappenden et al [105] showed that SCFA-supplemented TPN rapidly upregulated jejunal GLUT-2 mRNA (glucose transporter 2) and ileal GLUT-2 abundance and ileal proglucagon mRNA. Within the intestinal resection model, SCFAs may exert their trophic effect by extending the duration of increased proglucagon expression.…”