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

Abstract

Improved procedures for sample preparation and proteomic data analysis allowed us to identify 7700 different proteins in mouse small intestinal mucosa and calculate the concentrations of >5000 proteins. We compared protein concentrations of small intestinal mucosa from mice that 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. Eleven percent 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 β-oxidation, and steroid metabolism were also increased. Enzymes of glycolysis and pentose phosphate cycle were decreased, whereas proteins of the respiratory chain and of ATP synthase were increased. The protein concentrations of various nutrient transporters located in the enterocyte plasma membrane including the Na(+)-d-glucose cotransporter 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, which suggests 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.

Structure of, and functional insight into the GLUT family of membrane transporters

“…[158][159][160][161][162][163] In contrast, stress, a high-fat diet, and glucocorticoids inhibit GLUT2 trafficking to the brush border membrane. [164][165][166] Most recently, subcellular localization studies using live cell imaging demonstrated that GLUT2 is endocytosed through a caveolae-dependent mechanism, which is partially recovered in Rab11A-positive recycling endosomes. 99 However, what is still not entirely clear is the role that this transporter plays while it is transiently expressed at the cell surface.…”

Metabolic Adaptation of the Small Intestine to Short- and Medium-Term High-Fat Diet Exposure

“…High‐fat diet (HFD) feeding changes the functional properties of the small intestinal epithelium significantly. In particular enzymes involved in the fatty acid metabolism and oxidative phosphorylation pathways are substantially increased after 4 weeks of HFD exposure (de Wit et al, ; Wiśniewski et al, ). Also, we and others have shown that the systemic administration of fatty acid metabolism modulators induced an acute stimulation of fatty acid oxidation and ketogenesis in the jejunum but not in the liver (Uchida et al, ; Karimian Azari et al, ; Schober et al, ; Azari et al, ).…”

RS1 (Rsc1A1) deficiency limits cerebral SGLT1 expression and delays brain damage after experimental traumatic brain injury

“…turned out to represent cross-reactivity because they were removed after preabsorption of the antibody with the antigenic peptides but remained in SGLT1 À/À mice. Measuring SGLT1 mRNA abundance after TBI we ensured detection of SGLT1 specific signals although the abundance of SGLT1 mRNA in brain is four orders of magnitude lower compared to small intestine where SGLT1 is the most abundant transport protein in the brush-border membrane (Wisniewski et al 2015). Measuring mRNA abundance, we could relate the observed alterations to changes in transcription and/or mRNA stability.…”