Modulation of intestinal protein synthesis and protease mRNA by luminal and systemic nutrients

Abstract

Route of nutrient supply is important in regulation of intestinal protein metabolism, because total parenteral nutrition, compared with enteral feeding, leads to profound atrophy. Participation of the fractional rate of protein synthesis (Ks), their degradation in regulation of gut protein balance, and their possible modulation by specific nutrients are the focus of our work. We developed an in situ experimental system that allows controlled exposure of intestinal mucosa to nutrients systemically, luminally, or both. We examined the effects of systemic glucose and amino acid (AA) infusion in overnight-fasted piglets. Jejunal segments within each piglet were simultaneously, luminally perfused with solutions containing various AAs or glucose. Intravenous infusion of glucose increased mucosal Ks by 16% (P < 0.05), whereas intravenous infusion of AA had no effect on Ks. Systemic glucose infusion had no effect on mRNA levels for components of the ubiquitin-proteasome proteolytic pathway. However, levels of these mRNA were reduced by intravenous or luminal AA supply. This effect was greatest (-50%) when highest tissue concentrations of AAs were achieved by the simultaneous infusion of AA by both routes (P < 0.05). Our findings suggest that not only is the modulation of protein balance in the intestine in response to nutrients in part attributable to anabolic stimulation of protein synthesis initiated by the systemic appearance of glucose, but a fall in protein degradation is also a likely contributor. AAs appear to be a key factor required to reduce expression of genes connected with proteolysis.

Loss of exocrine pancreatic stimulation during parenteral feeding suppresses digestive enzyme expression and induces Hsp70 expression

“…These data are in agreement with those of other studies demonstrating that luminal nutrients are necessary for stimulating hormonal and/or neural regulation of digestive tissue maintenance and protein synthesis (1,4,11,15,19). The saline-infused orally fed group, which served as a surgical control, accumulated weight over the 7-day experiment; however, this was not to the extent of the nonsurgical control group.…”

Gut function and dysfunction in young pigs: physiology

“…This may be related to the fact that, at a similar protein to energy ratio, increasing fat content of the diet strongly stimulates protein synthesis in portal-drained viscera [67]. By contrast, recent data reported that AA provided luminally are a key factor required to reduce the expression of genes connected with intestinal proteolysis [1]. Mucosal protein synthesis can be increased by adding a colostrum extract to the diet [47].…”

Effect of Amino Acid Infusion on Human Postoperative Colon Protein Synthesis in Situ

“…40,43 Parenteral effects of amino acids on protein synthesis are less clear and may depend on technique, site, or species. Thus, amino acid infusion increased intestinal protein synthesis in dogs 44 but not in pigs 36,45 or human duodenum. 46 Considering our rigid study design (triple mucosal biopsies in the same subjects before and during amino acid infusion), our findings strongly support the idea that a potential anabolic effect of an increased basolateral amino acid supply at the gut does not imply a rise in intestinal protein synthesis.…”

“…33,34 However, this use does not necessarily reflect enhanced protein synthesis because decreased protein breakdown or accelerated amino acid oxidation is possible. With respect to protein synthesis, enteral protein feeding was without relevant effect in the jejunum of adult pigs, [35][36][37] or in the duodenum of adult man. 38 In contrast to whole proteins, enteral application of free amino acids seems to be more effective, although large amounts may be required.…”

“…38 In contrast to whole proteins, enteral application of free amino acids seems to be more effective, although large amounts may be required. After a short-term application (1.25 hours) of only small amounts (0.38 g/kg), gut protein synthesis did not rise in young pigs, 36 whereas significantly more enteral amino acids (Ͼ1 g/kg) increased small-bowel protein synthesis in dogs 39 and duodenal protein synthesis in man. 40 Such an enteral dose/effect relationship may also exist for specific amino acids such as glutamine, which, when given orally at a rate of 20 mg/kg per h, did not alter human enterocyte proliferation or duodenal protein synthesis.…”