how the intestinal peptide transporter pept-1 contributes to an obesity phenotype in caenorhabditits elegans肠肽转运蛋白如何pept-1导致的肥胖表现型caenorhabditits线虫.pdfVIP

How the Intestinal Peptide Transporter PEPT-1 Contributes to an Obesity Phenotype in Caenorhabditits elegans 1 1 3 1 1 1 Britta Spanier *, Katrin Lasch , Silke Marsch , Jacqueline Benner , Wenjuan Liao , Hao Hu , Hermine 2 3 1 Kienberger , Wolfgang Eisenreich , Hannelore Daniel ¨ ¨ 1 Abteilung Biochemie, ZIEL Research Center of Nutrition and Food Sciences, Technische Universitat Munchen, Freising, Germany, 2 Abteilung Bioanalytik, ZIEL Research ¨ ¨ ¨ ¨ ¨ Center of Nutrition and Food Sciences, Technische Universitat Munchen, Freising, Germany, 3 Lehrstuhl fur Biochemie, Technische Universitat Munchen, Garching, Germany 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-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 p