title: Mice lacking the intestinal peptide transporter display reduced energy intake and a subtle maldigestion/malabsorption that protects them from diet-induced obesity.
abstract: The intestinal transporter PEPT1 mediates the absorption of di- and tripeptides originating from breakdown of dietary proteins. Whereas mice lacking PEPT1 did not display any obvious changes in phenotype on a high-carbohydrate control diet (HCD), Pept1(-/-) mice fed a high-fat diet (HFD) showed a markedly reduced weight gain and reduced body fat stores. They were additionally protected from hyperglycemia and hyperinsulinemia. Energy balance studies revealed that Pept1(-/-) mice on HFD have a reduced caloric intake, no changes in energy expenditure, but increased energy content in feces. Cecal biomass in Pept1(-/-) mice was as well increased twofold on both diets, suggesting a limited capacity in digesting and/or absorbing the dietary constituents in the small intestine. GC-MS-based metabolite profiling of cecal contents revealed high levels and a broad spectrum of sugars in PEPT1-deficient mice on HCD, whereas animals fed HFD were characterized by high levels of free fatty acids and absence of sugars. In search of the origin of the impaired digestion/absorption, we observed that Pept1(-/-) mice lack the adaptation of the upper small intestinal mucosa to the trophic effects of the diet. Whereas wild-type mice on HFD adapt to diet with increased villus length and surface area, Pept1(-/-) mice failed to show this response. In search for the origin of this, we recorded markedly reduced systemic IL-6 levels in all Pept1(-/-) mice, suggesting that IL-6 could contribute to the lack of adaptation of the mucosal architecture to the diets.
authors.affiliation: Biochemistry, Technische Universität München, ZIEL Research Center of Nutrition and Food Sciences, Gregor-Mendel-Straße 2, D-85350 Freising, Germany.
authors.forename: Dominika
authors.initials: D
authors.lastname: Kolodziejczak
authors.forename: Britta
authors.initials: B
authors.lastname: Spanier
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.forename: Judith
authors.initials: J
authors.lastname: Kraiczy
authors.forename: Tamara
authors.initials: T
authors.lastname: Stelzl
authors.forename: Kurt
authors.initials: K
authors.lastname: Gedrich
authors.forename: Christian
authors.initials: C
authors.lastname: Scherling
authors.forename: Tamara
authors.initials: T
authors.lastname: Zietek
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
mesh_terms: D000818:Animals; D001823:Body Composition / Q000235:genetics; D001831:Body Temperature / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004032:Diet; D004063:Digestion / Q000235:genetics*; D004326:Drinking / Q000235:genetics; D004435:Eating / Q000235:genetics / Q000523:psychology; D002149:Energy Intake / Q000235:genetics*; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D005772:Gastrointestinal Transit / Q000235:genetics / Q000502:physiology; D050356:Lipid Metabolism / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008286:Malabsorption Syndromes / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D009929:Organ Size / Q000235:genetics / Q000502:physiology; D000074011:Peptide Transporter 1; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D012007:Rectum / Q000502:physiology; D027981:Symporters / Q000235:genetics / Q000502:physiology*
chemical_list: D000074011:Peptide Transporter 1; C082186:SLC15A1 protein, human; D027981:Symporters; D012313:RNA
keywords: PEPT1; cecal biomass; fecal energy; interleukin-6; morphological adaptation; sodium/hydrogen exchanger-3