Phenotype analysis of mice deficient in the peptide transporter PEPT2 in response to alterations in dietary protein intake

Abstract

The peptide transporter PEPT2 mediates cellular uptake of di- and tripeptides driven by an inwardly directed electrochemical proton gradient. In mammals PEPT2 is found in a variety of organs such as kidney, lung, brain, enteric nervous system, and mammary gland. Highest expression levels are observed in renal proximal tubules where PEPT2 contributes to reabsorption of filtered di- and tripeptides. To assess the physiological importance of the transporter in overall metabolism, we have generated a Pept2-/- mouse line that lacks a functional PEPT2 protein. Here we present data on body weight, organ weights, and blood pressure. Mice were then fed diets containing either 10, 20, or 30% (w/w) protein, and food and water intake rates as well as plasma and urine parameters were determined. In spite of PEPT2 expression in a variety of tissues, only subtle phenotypic changes were observed. Male PEPT2 null mice displayed lower bodyweight and lower relative heart weight, whereas, relative kidney weight was lower in female Pept2-/- mice. No differences were found in blood pressure. When fed diets with different protein contents, Pept2-/- mice adapted food intake to dietary protein content with higher consumption rates on low protein and reduced food intake rates on the high protein diet.

Beyond the Role of Dietary Protein and Amino Acids in the Prevention of Diet-Induced Obesity

“…Sympathetic activation [99] and increases in metabolic rate [87] were detected following water intake in humans. Secondly, animal studies showed that higher protein concentrations in experimental diets significantly enhanced water intake in mice [100], rats [101–103], and pigs [94] accompanied by higher urine volumes. Interestingly, mice fed high-protein diets exhibited higher liver water contents [91].…”

Profiling at mRNA, protein, and metabolite levels reveals alterations in renal amino acid handling and glutathione metabolism in kidney tissue ofPept2−/−mice

“…Recent clearance studies with the dipeptide glycyl-sarcosine in Pept2 Ϫ/Ϫ and wild-type mice established that PEPT2 indeed accounts for 86% of overall renal peptide reabsorption (25). Mice lacking the peptide transporter PEPT2 nevertheless display only very little phenotypic alterations (14,35). To assess to which extent this lack of a prominent phenotype in Pept2 Ϫ/Ϫ mice is caused by biological redundancy, a comprehensive analysis of mRNA, protein, and metabolite levels in the same kidney tissue samples of transporterdeficient and control animals was performed in combination with the assessment of urinary losses of amino acids and dipeptides.…”

Substrates of the human oligopeptide transporter hPEPT2

“…However, experiments demonstrated that PEPT2-null animals were healthy and fertile. In addition, neither clinical chemistry data obtained from plasma and urine samples nor general physiological measures indicated any significant metabolic perturbation (4,20,21). Therefore, the exact physiological role of PEPT2 warrants further studies.…”