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The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet.

Nässl AM, Rubio-Aliaga I, Sailer M, Daniel H - PLoS ONE (2011)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.

ABSTRACT
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.

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Changed plasma amino acids after 5 and 18 days on high-protein diet in Pept1−/− animals.By LC-MS/MS plasma amino acid concentrations of Pept1+/+ (wt) and Pept1−/− (ko) animals a high-protein (45% protein energy) diet were analyzed (n = 3–10). Plasma amino acid profiles of arginine (Arg), leucine (Leu) and the sum of all detectable amino acids (Sum) of Pept1−/− (ko) and Pept1+/+ (wt) animals on high-protein (HP) diet for 5 and 18 days are depicted. Data are presented as mean±SD. (•) indicate outlier. *P<0.05, $P<0.01, §P<0.001.
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pone-0026407-g004: Changed plasma amino acids after 5 and 18 days on high-protein diet in Pept1−/− animals.By LC-MS/MS plasma amino acid concentrations of Pept1+/+ (wt) and Pept1−/− (ko) animals a high-protein (45% protein energy) diet were analyzed (n = 3–10). Plasma amino acid profiles of arginine (Arg), leucine (Leu) and the sum of all detectable amino acids (Sum) of Pept1−/− (ko) and Pept1+/+ (wt) animals on high-protein (HP) diet for 5 and 18 days are depicted. Data are presented as mean±SD. (•) indicate outlier. *P<0.05, $P<0.01, §P<0.001.

Mentions: To assess alterations in systemic amino acid levels of mice fed diets with different protein contents, we analyzed plasma samples by LC-MS/MS. As a highly consistent and genotype-specific finding, we observed an almost two-fold increase in plasma levels of arginine in Pept1−/− mice on both, C (ko: 90±29.8 µmol/l vs. wt: 44.8±22.8 µmol/l, P = 0.002) and HP diet (ko: 96.9±42.6 µmol/l vs. wt: 53.1±19.1 µmol/l, P = 0.008) after 5 days (Table S1). Genotype-independent effects of the diets were found for valine, leucine, isoleucine, but also for alpha-aminobutyric acid and glutamine with significantly increased levels in plasma obtained from animals on the HP diet. Decreased plasma levels were found for anserine and hydroxyproline. After 18 days of feeding, alpha-aminobutyric acid levels as well as leucine and isoleucine levels remained increased (Table S2) whereas glutamine and ethanolamine showed higher levels in animals on control than on HP diet irrespective of genotypes. Representative plasma amino acid levels at days 5 and 18 when feeding the HP diet are summarized in Figure 4.


The intestinal peptide transporter PEPT1 is involved in food intake regulation in mice fed a high-protein diet.

Nässl AM, Rubio-Aliaga I, Sailer M, Daniel H - PLoS ONE (2011)

Changed plasma amino acids after 5 and 18 days on high-protein diet in Pept1−/− animals.By LC-MS/MS plasma amino acid concentrations of Pept1+/+ (wt) and Pept1−/− (ko) animals a high-protein (45% protein energy) diet were analyzed (n = 3–10). Plasma amino acid profiles of arginine (Arg), leucine (Leu) and the sum of all detectable amino acids (Sum) of Pept1−/− (ko) and Pept1+/+ (wt) animals on high-protein (HP) diet for 5 and 18 days are depicted. Data are presented as mean±SD. (•) indicate outlier. *P<0.05, $P<0.01, §P<0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198773&req=5

pone-0026407-g004: Changed plasma amino acids after 5 and 18 days on high-protein diet in Pept1−/− animals.By LC-MS/MS plasma amino acid concentrations of Pept1+/+ (wt) and Pept1−/− (ko) animals a high-protein (45% protein energy) diet were analyzed (n = 3–10). Plasma amino acid profiles of arginine (Arg), leucine (Leu) and the sum of all detectable amino acids (Sum) of Pept1−/− (ko) and Pept1+/+ (wt) animals on high-protein (HP) diet for 5 and 18 days are depicted. Data are presented as mean±SD. (•) indicate outlier. *P<0.05, $P<0.01, §P<0.001.
Mentions: To assess alterations in systemic amino acid levels of mice fed diets with different protein contents, we analyzed plasma samples by LC-MS/MS. As a highly consistent and genotype-specific finding, we observed an almost two-fold increase in plasma levels of arginine in Pept1−/− mice on both, C (ko: 90±29.8 µmol/l vs. wt: 44.8±22.8 µmol/l, P = 0.002) and HP diet (ko: 96.9±42.6 µmol/l vs. wt: 53.1±19.1 µmol/l, P = 0.008) after 5 days (Table S1). Genotype-independent effects of the diets were found for valine, leucine, isoleucine, but also for alpha-aminobutyric acid and glutamine with significantly increased levels in plasma obtained from animals on the HP diet. Decreased plasma levels were found for anserine and hydroxyproline. After 18 days of feeding, alpha-aminobutyric acid levels as well as leucine and isoleucine levels remained increased (Table S2) whereas glutamine and ethanolamine showed higher levels in animals on control than on HP diet irrespective of genotypes. Representative plasma amino acid levels at days 5 and 18 when feeding the HP diet are summarized in Figure 4.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus