How the intestinal peptide transporter PEPT-1 contributes to an obesity phenotype in Caenorhabditits elegans
| Autor: | Wolfgang Eisenreich, Hao Hu, Silke Marsch, Hannelore Daniel, Jacqueline Benner, Wenjuan Liao, Hermine Kienberger, Katrin Lasch, Britta Spanier |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Chromatography
Gas Physiology Intracellular pH lcsh:Medicine Peptide Tripeptide Biology Fatty Acids Nonesterified Peptide Transporter 1 chemistry.chemical_compound Nutrition/Obesity Animals Obesity Intestinal Mucosa Caenorhabditis elegans lcsh:Science Molecular Biology Nuclear Magnetic Resonance Biomolecular Fatty acid synthesis Oligonucleotide Array Sequence Analysis chemistry.chemical_classification Multidisciplinary Symporters lcsh:R Peroxisome Nutrition/Deficiencies Amino acid Phenotype chemistry Biochemistry Peptide transport lcsh:Q Polyunsaturated fatty acid Research Article |
| Zdroj: | PLoS ONE, Vol 4, Iss 7, p e6279 (2009) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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-13C]-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 β-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. |
| Databáze: | OpenAIRE |
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