Rates Of Mucosal Protein Synthesis Research Articles

Enteral feeding induces profound early intestinal adaptation in a neonatal piglet model of short bowel syndrome

Our objective was to characterize small intestinal (SI) adaptation in a novel piglet model. Piglets (n = 32, 12–13 d old) were randomized to 1) 80% SI resection with total parenteral nutrition (TPN) feeding (R‐TPN), 2) 80% SI resection with TPN + enteral feeding (R‐EN) or 3) sham SI transection with TPN + enteral feeding (Sham‐EN). In R pigs, the distal 100 cm of ileum (residual SI) and 30 cm of proximal SI was left intact. All pigs received TPN after surgery. R‐EN and Sham‐EN piglets also received continuous gastric infusions of elemental diet starting on d 3 (40:60 TPN:EN). Piglets were killed 4, 6 or 10 d post‐surgery. Cell proliferation in residual SI, assessed by incorporation of 5‐bromo‐2′‐deoxyuridine (BrdU) was significantly greater in R‐EN animals (29.5 ± 4.7 %) compared to Sham‐EN (13.63 ± 5.7 %) and R‐TPN (12.97 ± 8.9 %) animals at d 4 (P<0.05). R‐EN at d 4 also had higher rates of mucosal protein synthesis than Sham‐EN (P<0.001) and R‐TPN animals (P<0.05), (87.2 ± 3.2 vs 53.2 ± 2.1 and 59.7 ± 9.7 %/d, respectively). Villous height and crypt depth were greater in R‐EN animals compared to Sham‐EN animals at d 6 and 10 (p<0.05). Less than 24 h of enteral feeding increased rates of cell proliferation and protein synthesis; this translated into greater villous height and crypt depth only 2 d later. This piglet model will be very useful in assessing the efficacy of nutritional interventions targeting SI adaptation. (SickKids Foundation)

W1190 Gastrointestinal Mucosal Protein Synthesis Rates in Pediatric Crohn's Disease

W1190 Gastrointestinal Mucosal Protein Synthesis Rates in Pediatric Crohn's Disease

Feeding an Elemental Diet vs a Milk‐Based Formula Does Not Decrease Intestinal Mucosal Growth in Infant Pigs

We previously showed that the level of enteral nutrient intake determines the rate of intestinal growth in piglets. Our objective was to determine whether providing enteral nutrition in the form of elemental nutrients (glucose, amino acids, lipid [ED]) rather than cow's milk formula (lactose, protein, lipid [FORM]) reduces small intestinal growth and lactase activity. Three-week-old piglets were fed either ED (n = 7) intragastrically or FORM (n = 6) orally for 6 days. Intestinal protein and DNA masses, villus height, and crypt depth were not different in ED and FORM pigs. Crypt cell proliferation, measured by in vivo bromodeoxyuridine labeling, was significantly (p < .05) higher (+37%) in ED than in FORM pigs. Rates of mucosal protein synthesis (%/d), measured by in vivo 2H-leucine incorporation, were higher (p < .05) in ED than FORM (147 vs 89) pigs. Circulating concentrations (pmol/L) of the intestinotrophic peptide, glucagon-like peptide-2 (GLP-2), were also higher (p < .05) in ED than in FORM (148 vs 87) pigs. The mean lactase-specific activity (micromol/min/g) in proximal and distal segments was higher (p < .05) in FORM than in ED (124 vs 58) pigs. We conclude that intestinal mucosal growth and villus morphology are similar in pigs fed ED and FORM, despite higher cell proliferation and protein synthesis rates and lower lactase activity with ED. This implies that elemental diets may be as trophic as polymeric formulas to simultaneously provide nutrition and a stimulus for intestinal growth during bowel rest.

Regional variation in small intestinal (SI) mucosal protein synthesis and the effect of colectomy on whole-body protein turnover

AIM: We have measured protein synthesis in the SI mucosa to assess possible differences in the rates of mucosal protein synthesis between the proximal and distal regions of the SI in ileostomates and to assess the effect of colectomy on protein turnover. METHODS: Six subjects with ileostomy were studied (mean _+ SD) (46 _+ 21y, 65 _+ 14kg, 169 + 6cm) and the results compared with 8 normal volunteer subjects (44_+15y, 71_+ 12kg, 171 _+ 1 lcm). The ileostomy in these subjects allowed practical access to the distal region of the SI. The terminal ileum was histologically normal in all ileostomy subjects studied. All subjects received primed, continuous IV infusions of L-[1-13C] leucine after an overnight fast. After 4h of tracer infusion jejunal and ileal biopsies were obtained. RESULTS: The results are presented as means _+ SD. Rates of jejunal and ileal mucosal protein synthesis were 2.14 _+ 0.2 and 1.2 + 0.2 (%h -l) respectively; jejunal vs. ileal p<0.001. The whole-body protein turnover rate was, ileostomates vs controls; 145 _+ 15vs. 196 + 44umol/kg/h, p<0.01. In the SI mucosa of subjects with ileostomy the rates of protein synthesis were different at different levels, being significantly higher at the proximal level and lower at the distal level. The plasma leucine enrichment increased by 28% and plasma ketoisocaproate enrichment by 26% with a significantly reduced whole-body protein turnover. CONCLUSION: These changes are probably related to the reduction in the size of the plasma amino acid compartment or reduced lean tissue mass following colectomy and indicate that the colon has a significant contribution to the whole-body protein turnover.

Increased rates of duodenal mucosal protein synthesis in vivo in patients with untreated coelia disease.

A robust, reproducible method for the measurement of protein synthesis in the gastrointestinal mucosa was applied to investigate possible differences between the rate of duodenal mucosal protein synthesis in coeliac patients and normal control subjects. Eight patients, means (SD) (51 (10) years, 57 (11) kg, 160 (6) cm) with newly diagnosed untreated coeliac disease and seven control subjects (48 (11) years, 71.5 (12) kg, 172 (10) cm) received primed, continuous, intragastric (IG) and intravenous (i.v.) infusions of L-[1-13C]leucine and L-[1-13C]valine after an overnight fast. Distal duodenal biopsy specimens were obtained at endoscopy performed after 240 minutes of infusion. Protein synthesis was calculated from protein labelling relative to intracellular free amino acid enrichment, after appropriate mass spectrometric measurements. Rates of duodenal protein synthesis were significantly greater in coeliac patients than in control subjects (i.v. tracer, coeliac v control, 3.58 (0.45) v 2.26 (0.22)%/h, p< 0.05; IG tracer, 6.25 (0.97) v 2.34 (0.52)%/h respectively, p < 0.01). The rates of mucosal protein synthesis calculated on the basis of the tracer infused via the intragastric route were higher in patients with coeliac disease than in control subjects. Tissue protein/DNA ratios were significantly reduced in coeliac patients (coeliac v control, 9.2 (1.6) mg/micrograms v 13.0 (2.2) mg/micrograms respectively, p < 0.05) suggesting smaller mucosal cell size in coeliac patients. Despite the villous atrophy and reduced cell size observed in coeliac disease, the rates of mucosal protein synthesis are considerably increased. These results suggest that a high rate of protein synthesis may be adaptive to a high rate of protein breakdown or mucosal cell loss in coeliac patients.

Gut mucosal protein synthesis measured using intravenous and intragastric delivery of stable tracer amino acids

We measured the rates of mucosal protein synthesis during the simultaneous delivery of [1-13C]leucine and [1-13C]valine delivered either intragastrically or intravenously to investigate any influence of the route of supply of the tracers. Dependent on the route, there were marked differences in the gradient of labeling between the plasma and intramucosal leucine and valine; i.e., for intravenous tracers the ratio was 1.73 +/- 0.16, but for intragastric tracers it was 0.65 +/- 0.12 (P < 0.05). Incorporation of intravenous tracer into mucosal protein was linear with time, and irrespective of tracer route, the calculated fractional rates of protein synthesis were identical when based on the intracellular labeling of the leucine or valine tracer, i.e., with intravenous 2.58 +/- 0.32%/h and with intragastric 2.45 +/- 0.36%/h. The results demonstrate that a robust and reproducible method of measurement of gastrointestinal mucosal protein synthesis has been developed and that use of either intragastric or intravenous routes of tracer administration gives comparable results. The high rates measured suggest that the gastrointestinal mucosa contributes substantially to whole body protein synthesis in normal healthy subjects.

Effect of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract in rats.

1. In a previous study we found that the protein synthesis rate was increased by 50-60% in the mucosa of the jejunum and ileum during sepsis in rats. It is not known if sepsis affects protein turnover in other parts of the gastrointestinal tract as well. 2. In the present study, the influence of sepsis on mucosal protein synthesis in different parts of the gastrointestinal tract, from the stomach to the rectum, was determined in rats. 3. Sepsis was induced by caecal ligation and puncture; control rats underwent sham-operation. Protein synthesis rate was measured in vivo after administration of a flooding dose of [14C]leucine. 4. Basal mucosal protein synthesis rates were lower in the colon than in the rest of the gastrointestinal tract. Sixteen hours after caecal ligation and puncture, the protein synthesis rates were increased by 40-85% in the mucosa of the small and large intestine and the rectum, whereas in the gastric mucosa, the protein synthesis rate was reduced by approximately 40%. 5. The results suggest that mucosal protein synthesis rates differ in the various regions of the gastrointestinal tract, and that the metabolic response to sepsis is different in the stomach than in the rest of the gastrointestinal tract. The finding of a reduced protein synthesis rate in the gastric mucosa may partly explain the tendency to gastric stress ulcers and bleeding seen clinically in sepsis.

In vivo rates of mucosal protein synthesis in patients with Barrett’s oesophagus

In vivo rates of mucosal protein synthesis in patients with Barrett’s oesophagus

Stimulation of jejunal mucosal protein synthesis by luminal glucose: Effects with luminal and vascular leucine in fed and fasted rats

This study was conducted to determine whether short-term (1.75 h) luminal glucose perfusion increases the mucosal protein synthesis rate in rat small intestine. A luminal perfusate containing 56 mM glucose was compared with a control perfusate containing mannitol in two jejunal segments constructed in the same animal. Mucosal protein synthesis rates were determined when the tracer amino acid was administered intravenously and intraluminally. The results indicated that luminal glucose perfusion rapidly stimulated mucosal protein synthesis in the fed state by 20% and 37% with the labeled amino acid derived from the vascular and luminal compartment, respectively. A 16-h fast abolished the stimulatory effect of glucose when the labeled amino acid was given intravascularly but not intraluminally. These effects of glucose could be ascribed to a direct alteration of mucosal metabolism rather than to indirect systemic effects.

Stimulation of jejunal Mucosal Protein Synthesis by Luminal Glucose: Effects With Luminal and Vascular Leucine in Fed and Fasted Rats

This study was conducted to determine whether short-term (1.75 h) luminal glucose perfusion increases the mucosal protein synthesis rate in rat small intestine. A luminal perfusate containing 56 mM glucose was compared with a control perfusate containing mannitol in two jejunal segments constructed in the same animal. Mucosal protein synthesis rates were determined when the tracer amino acid was administered intravenously and intraluminally. The results indicated that luminal glucose perfusion rapidly stimulated mucosal protein synthesis in the fed state by 20% and 37% with the labeled amino acid derived from the vascular and luminal compartment, respectively. A 16-h fast abolished the stimulatory effect of glucose when the labeled amino acid was given intravascularly but not intraluminally. These effects of glucose could be ascribed to a direct alteration of mucosal metabolism rather than to indirect systemic effects.