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American Chemical Society, Journal of Proteome Research, 1(14), p. 353-365, 2014

DOI: 10.1021/pr500833v

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The Impact of High-Fat Diet on Metabolism and Immune Defense in Small Intestine Mucosa

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Improved procedures for sample preparation and proteomic data analysis allowed to identify 7,700 different proteins in mouse small intestinal mucosa and to calculate the concentrations of >5,000 proteins. We compared protein concentrations of small intestinal mucosa from mice which were fed for two months with normal diet (ND) containing 34.4% carbohydrates, 19.6% protein and 3.3% fat or high fat diet (HFD) containing 25.3% carbohydrates, 24.1% protein and 34.6% fat. 11% of the quantified proteins were significantly different between ND and HFD. After HFD, we observed an elevation of proteins involved in protein synthesis, protein N-glycosylation, and vesicle trafficking. Proteins engaged in fatty acid absorption, fatty acid ?-oxidation, and steroid metabolism were also increased. Enzymes of glycolysis and pentose phosphate cycle were decreased whereas proteins of the respiratory chain and of the ATP synthase were increased. The protein concentrations of various nutrient transporters located in the enterocyte plasma membrane including the Na+-D-glucose SGLT1, the passive glucose transporter GLUT2 and the H+-peptide cotransporter PEPT1 were decreased. The concentration of the Na+,K+-ATPase which turned out to be the most strongly expressed enterocyte transporter, was also decreased. HFD also induced concentration changes of drug transporters and of enzymes involved in drug metabolism suggesting effects of HFD on pharmacokinetics and toxicities. Finally, we observed down-regulation of antibody subunits and of components of the major histocompatibility complex II that may reflect impaired immune defense and immune tolerance in HFD. Our work shows dramatic changes in functional proteins of small intestine mucosa upon excessive fat consumption.