The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet.
High-protein diets are effective in achieving weight loss which is mainly explained by increased satiety and thermogenic effects. Recent studies suggest that the effects of protein-rich diets on satiety could be mediated by amino acids like leucine or arginine. Although high-protein diets require increased intestinal amino acid absorption, amino acid and peptide absorption has not yet been considered to contribute to satiety effects. We here demonstrate a novel finding that links intestinal peptide transport processes to food intake, but only when a protein-rich diet is provided. When mice lacking the intestinal peptide transporter PEPT1 were fed diets containing 8 or 21 energy% of protein, no differences in food intake and weight gain were observed. However, upon feeding a high-protein (45 energy%) diet, Pept1(-/-) mice reduced food intake much more pronounced than control animals. Although there was a regain in food consumption after a few days, no weight gain was observed which was associated with a reduced intestinal energy assimilation and increased fecal energy losses. Pept1(-/-) mice on high-protein diet displayed markedly reduced plasma leptin levels during the period of very low food intake, suggesting a failure of leptin signaling to increase energy intake. This together with an almost two-fold elevated plasma arginine level in Pept1(-/-) but not wildtype mice, suggests that a cross-talk of arginine with leptin signaling in brain, as described previously, could cause these striking effects on food intake.
ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.
Anna-Maria
AM
Nässl
Isabel
I
Rubio-Aliaga
Manuela
M
Sailer
Hannelore
H
Daniel
D000596:Amino Acids / Q000097:blood; D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D018826:CD13 Antigens / Q000378:metabolism; D002151:Calorimetry; D002853:Chromatography, Liquid; D004044:Dietary Proteins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000074011:Peptide Transporter 1; D027981:Symporters / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
D000596:Amino Acids; D004044:Dietary Proteins; D000074011:Peptide Transporter 1; C489941:Slc15a1 protein, mouse; D027981:Symporters; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D018826:CD13 Antigens