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


RESULTS
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.
Spanier
Britta
B
Abteilung Biochemie, ZIEL Research Center of Nutrition and Food Sciences, Technische Universität München, Freising, Germany. spanier@wzw.tum.de
Lasch
Katrin
K
Marsch
Silke
S
Benner
Jacqueline
J
Liao
Wenjuan
W
Hu
Hao
H
Kienberger
Hermine
H
Eisenreich
Wolfgang
W
Daniel
Hannelore
H
D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D002849:Chromatography, Gas; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D000074011:Peptide Transporter 1; D010641:Phenotype; D027981:Symporters / Q000235:genetics / Q000502:physiology*
D005230:Fatty Acids, Nonesterified; D000074011:Peptide Transporter 1; D027981:Symporters