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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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Pept1−/− animals on high-protein diet show major changes in metabolic parameters.Metabolic parameters of male mice on low-protein (LP  = 8% protein energy), control (C  = 21% protein energy) and high-protein (HP = 45% protein energy) diet were determined in Pept1+/+ (wt) and Pept1−/− (ko) animals. During 5 days on the different diets, food intake (A), weight (B), and feces excretion (C) were determined (n = 10). Data are presented as mean±SEM. *P<0.05, $P<0.01, §P<0.001.
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pone-0026407-g001: Pept1−/− animals on high-protein diet show major changes in metabolic parameters.Metabolic parameters of male mice on low-protein (LP  = 8% protein energy), control (C  = 21% protein energy) and high-protein (HP = 45% protein energy) diet were determined in Pept1+/+ (wt) and Pept1−/− (ko) animals. During 5 days on the different diets, food intake (A), weight (B), and feces excretion (C) were determined (n = 10). Data are presented as mean±SEM. *P<0.05, $P<0.01, §P<0.001.

Mentions: Determination of food intake and body weight changes in Pept1−/− mice fed for 5 days a LP or C diet did not show any significant alterations when compared to wildtype animals. However when animals were provided with a HP diet, food intake rates immediately declined in all animals but more pronounced in Pept1−/− animals (Figure 1). Whereas wildtype animals increased food consumption again after 2 days, Pept1−/− mice reduced food intake even further over 4 days (Figure 1A). This led in Pept1−/− animals also to a decrease in body weight (Figure 1B) and reduced feces excretion (Figure 1C). No differences in water consumption were observed, neither between diets nor genotypes (data not shown). A second feeding trial conducted over a 18 day period revealed a similar initial major reduction in food intake for 4 days in Pept1−/− mice while animals thereafter increased food consumption to reach the same intake rates as observed in wildtype animals (Figure 2A), yet, they failed to show any significant weight gain over the entire feeding trial (Figure 2B).


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)

Pept1−/− animals on high-protein diet show major changes in metabolic parameters.Metabolic parameters of male mice on low-protein (LP  = 8% protein energy), control (C  = 21% protein energy) and high-protein (HP = 45% protein energy) diet were determined in Pept1+/+ (wt) and Pept1−/− (ko) animals. During 5 days on the different diets, food intake (A), weight (B), and feces excretion (C) were determined (n = 10). Data are presented as mean±SEM. *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-g001: Pept1−/− animals on high-protein diet show major changes in metabolic parameters.Metabolic parameters of male mice on low-protein (LP  = 8% protein energy), control (C  = 21% protein energy) and high-protein (HP = 45% protein energy) diet were determined in Pept1+/+ (wt) and Pept1−/− (ko) animals. During 5 days on the different diets, food intake (A), weight (B), and feces excretion (C) were determined (n = 10). Data are presented as mean±SEM. *P<0.05, $P<0.01, §P<0.001.
Mentions: Determination of food intake and body weight changes in Pept1−/− mice fed for 5 days a LP or C diet did not show any significant alterations when compared to wildtype animals. However when animals were provided with a HP diet, food intake rates immediately declined in all animals but more pronounced in Pept1−/− animals (Figure 1). Whereas wildtype animals increased food consumption again after 2 days, Pept1−/− mice reduced food intake even further over 4 days (Figure 1A). This led in Pept1−/− animals also to a decrease in body weight (Figure 1B) and reduced feces excretion (Figure 1C). No differences in water consumption were observed, neither between diets nor genotypes (data not shown). A second feeding trial conducted over a 18 day period revealed a similar initial major reduction in food intake for 4 days in Pept1−/− mice while animals thereafter increased food consumption to reach the same intake rates as observed in wildtype animals (Figure 2A), yet, they failed to show any significant weight gain over the entire feeding trial (Figure 2B).

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