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How the intestinal peptide transporter PEPT-1 contributes to an obesity phenotype in Caenorhabditits elegans.


ABSTRACT: BACKGROUND: Amino acid absorption in the form of di- and tripeptides is mediated by the intestinal proton-coupled peptide transporter PEPT-1 (formally OPT-2) in Caenorhabditits elegans. Transporter-deficient animals (pept-1(lg601)) show impaired growth, slowed postembryonal development and major changes in amino acid status. PRINCIPAL FINDINGS: Here we demonstrate that abolished intestinal peptide transport also leads to major metabolic alterations that culminate in a two fold increase in total body fat content. Feeding of C. elegans with [U-(13)C]-labelled E. coli revealed a decreased de novo synthesis of long-chain fatty acids in pept-1(lg601) and reduced levels of polyunsaturated fatty acids. mRNA profiling revealed increased transcript levels of enzymes/transporters needed for peroxisomal beta-oxidation and decreased levels for those required for fatty acid synthesis, elongation and desaturation. As a prime and most fundamental process that may account for the increased fat content in pept-1(lg601) we identified a highly accelerated absorption of free fatty acids from the bacterial food in the intestine. CONCLUSIONS: The influx of free fatty acids into intestinal epithelial cells is strongly dependent on alterations in intracellular pH which is regulated by the interplay of PEPT-1 and the sodium-proton exchanger NHX-2. We here provide evidence for a central mechanism by which the PEPT-1/NHX-2 system strongly influences the in vivo fat content of C. elegans. Loss of PEPT-1 decreases intestinal proton influx leading to a higher uptake of free fatty acids with fat accumulation whereas loss of NHX-2 causes intracellular acidification by the PEPT-1 mediated proton/dipeptide symport with an almost abolished uptake of fatty acids and a lean phenotype.

SUBMITTER: Spanier B 

PROVIDER: S-EPMC2708923 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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How the intestinal peptide transporter PEPT-1 contributes to an obesity phenotype in Caenorhabditits elegans.

Spanier Britta B   Lasch Katrin K   Marsch Silke S   Benner Jacqueline J   Liao Wenjuan W   Hu Hao H   Kienberger Hermine H   Eisenreich Wolfgang W   Daniel Hannelore H  

PloS one 20090721 7


<h4>Background</h4>Amino acid absorption in the form of di- and tripeptides is mediated by the intestinal proton-coupled peptide transporter PEPT-1 (formally OPT-2) in Caenorhabditits elegans. Transporter-deficient animals (pept-1(lg601)) show impaired growth, slowed postembryonal development and major changes in amino acid status.<h4>Principal findings</h4>Here we demonstrate that abolished intestinal peptide transport also leads to major metabolic alterations that culminate in a two fold incre  ...[more]

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