Short-chain fatty acids and total parenteral nutrition affect intestinal gene expression.
BACKGROUND
The supplementation of total parenteral nutrition (TPN) formulas with short-chain fatty acids (SCFAs) increases glucose uptake and the expression of glucose transporters in parenterally fed animals. Several signals may be involved in intestinal adaptation; however, increased messenger RNA (mRNA) levels for proglucagon and several early-response genes, including c-myc and c-fos, are seen in animals receiving SCFA-supplemented TPN. Although the effects of a mixture of SCFAs are well documented, the relative contribution of individual SCFAs is unknown. Butyrate is a preferred fuel of colonocytes, with documented effects on cellular proliferation and gene expression. Accordingly, this study was undertaken to determine the relative role of butyrate in initiating an adaptive response in nonresected rats receiving TPN.


METHODS
Animals received standard TPN for 66 hours, followed by 6 hours of either standard TPN, TPN supplemented with a mixture of SCFAs (acetate, propionate, and butyrate, 60 mmol/L total), or TPN supplemented with butyrate alone (9 mmol/L). An oral control group was fed an elemental diet, similar in macronutrient content to the TPN, so that all animals received the same amount of energy daily.


RESULTS
SCFAs increased ileal glucose transporter 2 (GLUT2) mRNA expression compared with the orally fed group. SCFAs also increased proglucagon mRNA expression compared with the TPN group. No changes in Na+K(+)-adenosine triphosphatase or early-response gene expression were found in this study.


CONCLUSIONS
In a rat model of TPN, the use of 9 mmol/L butyrate did not have the same effect on GLUT2 and proglucagon expression as a 60-mmol/L mixture of SCFAs. This suggests that the effect of a mixture of SCFAs on intestinal gene expression is not butyrate specific.
Drozdowski
Laurie A
LA
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Canada. lad2@ualberta.ca
Dixon
Walter T
WT
McBurney
Michael I
MI
Thomson
Alan B R
AB
D000818:Animals; D015152:Blotting, Northern; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology; D005232:Fatty Acids, Volatile / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D005934:Glucagon / Q000235:genetics* / Q000378:metabolism; D051273:Glucose Transporter Type 2; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D010289:Parenteral Nutrition, Total; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002087:Butyrates; D005232:Fatty Acids, Volatile; D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D052336:Proglucagon; D005934:Glucagon