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Fatty acid binding proteins appear to guide intestinal adaptation Human patients can sometimes adapt to having significant portions of their small intestine removed. When intestinal adaptation occurs, the rest of the small intestine thickens, increasing its capacity to absorb nutrition. This gradual process can eventually allow a patient to resume eating solid food and stop receiving nutrition intravenously. Now, in JPR (DOI 10.1021/pr900976f), a team of researchers from Prince Henry’s Institute of Medical Research and Murdoch Children’s Research Institute (both in Australia) report one of the first proteomic analyses of an animal model of intestinal adaptation. The authors describe >60 proteins that change expression in pigs’ intestinal cells in response to resection of the small intestine. In particular, the authors identify two fatty acid binding proteins, L-FABP and FABP-6, as markers that appear to mirror intestinal cell growth. One of the researchers’ goals was to find markers that can help doctors predict which patients will adapt well and which will adapt poorly to resection, says the team’s leader, Julie Bines. Such clinical markers could also help doctors assess treatments, such as growth hormones and specialized feeding formulas that are designed to promote intestinal adaptation. Reasons for partial small intestine removal include congenital defects in children and inflammatory bowel disease, trauma, or cancer in adults. In premature infants, necrotizing enterocolitis is one of the most common gastrointestinal emergencies. Having an insufficient area in the small intestine for nutrient absorption results in short bowel syndrome: a combination of malnutrition and diarrhea often lethal when encountered in childhood. Because of potential complications, intestinal transplants are seen as a last resort when a patient’s intestines do not adapt, Bines says. At the same time, prolonged periods of supplying nutrition
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directly into the bloodstream carry a risk of sepsis and liver disease. “The changes in the intestine begin within hours but can take up to two years,” she says. “All the clinical evidence says that if a patient is going to require an intestinal transplant, it is better to transplant early.” Bines’ team removed 75% of the small intestine from four-week-old pigs and
Adaptation to intestinal resection. Immunohistochemistry shows the differential expression of the fatty acid binding protein L-FABP in pigs’ intestinal tissue sections following small bowel resection.
allowed them six weeks to recover. They compared proteins from the pigs’ remaining intestinal tissue against tissue from pigs that had undergone surgery but without bowel removal. The proteins were labeled with fluorescent dyes and analyzed on 2D gels. The team focused on fatty acid binding proteins, examining their expression independently by Western blot and im-
Journal of Proteome Research • Vol. 9, No. 3, 2010
munohistochemistry. The expression of L-FABP and FABP-6 increased in the intestinal tissue of resected animals, and the number of cells staining positive for these proteins also increased in intestinal villi. “The increase in fatty acid binding proteins suggests that intestinal tissues are trying hard to extract as much nutrition as possible,” Bines says. The team observed an increase in serum triglycerides and serum bile acids in resected animals. Such an increase is not consistent with decreased ability to absorb lipids from the gut. Bines notes that the finding may reflect compensatory metabolic changes in the liver or other tissues. The authors observe increased FABP-6 expression as early as two weeks after surgery in resected animals. They suggest that FABP-6, a modulator of intestinal cell growth known to be regulated by bile acids, may act as a bile acid sensor. “This was a good first look, but there’s a lot more going on besides changes in fatty acid binding proteins,” notes Leonard Augenlicht at Albert Einstein College of Medicine. He adds that additional proteome-guided analysis of signaling pathways and the influence of diet on intestinal adaptation would be valuable. “This is an important contribution to the understanding of the mechanism of intestinal adaptation,” says Chris Erwin at Washington University Medical School. “The authors’ proteomic analysis of intestinal adaptation in pigs complements RNA array work in mice showing similar classes and levels of gene and protein expression, although gene lists between the two systems differ.” Bines says that ideally, clinical markers would come from blood, stool, or bile secretions and not directly from intestinal tissue. “Right now, doctors monitor patients after intestinal resection by assessing factors such as diarrhea and weight gain,” she says. “If there could be a way to assess progress while avoiding intestinal biopsies, it could point the way to improved clinical outcomes.” —Quinn Eastman
10.1021/pr9012128
© 2010 American Chemical Society
