title: Digested wheat gluten inhibits binding between leptin and its receptor.
abstract: BACKGROUND
  Leptin resistance is considered a primary risk factor for obesity. It has been hypothesized that dietary cereal grain protein could cause leptin resistance by preventing leptin from binding to its receptor. Non-degraded dietary wheat protein has been found in human serum at a mean level of 41 ng/mL. Here, we report our findings from testing whether enzymatically digested gluten from wheat prevents leptin from binding to the leptin receptor in vitro. Gluten from wheat was digested with pepsin and trypsin under physiological conditions. Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin-filter or by heat treatment at 100°C for 30 min. Binding to the leptin receptor of leptin mixed with gluten digest at a series of concentrations was measured using surface plasmon resonance technology.
  
  
  RESULTS
  Binding of the gluten digest to the leptin receptor was not detected. Spin-filtered gluten digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at a gluten digest concentration of ~10 ng/mL. Heat-treated gluten digest did not inhibit leptin binding.
  
  
  CONCLUSIONS
  Digested wheat gluten inhibits binding of leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The inhibition is significant at clinically relevant concentrations and could therefore serve as a novel pathway to investigate to understand the molecular basis of leptin resistance, obesity and associated disorders.
authors.affiliation: Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden. Tommy.Jonsson@med.lu.se.
authors.forename: Tommy
authors.initials: T
authors.lastname: Jönsson
authors.affiliation: Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden. Ashfaque.Memon@med.lu.se.
authors.forename: Ashfaque A
authors.initials: AA
authors.lastname: Memon
authors.affiliation: Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden. Kristina.Sundquist@med.lu.se.
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundquist
authors.affiliation: Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Malmö, Sweden. Jan.Sundquist@med.lu.se.
authors.forename: Jan
authors.initials: J
authors.lastname: Sundquist
authors.affiliation: Department of Plant and Environmental Science, University of Copenhagen, DK-1871, Frederiksberg C, Denmark. sto@plen.ku.dk.
authors.forename: Stefan
authors.initials: S
authors.lastname: Olsson
authors.affiliation: Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark. a.nalla@hotmail.com.|The Danish Diabetes Academy, Odense University Hospital, Odense, Denmark. a.nalla@hotmail.com.
authors.forename: Amarnadh
authors.initials: A
authors.lastname: Nalla
authors.affiliation: Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden. MikaelCBauer@gmail.com.
authors.forename: Mikael
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden. Sara.Linse@biochemistry.lu.se.
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
mesh_terms: D004044:Dietary Proteins / Q000378:metabolism / Q000494:pharmacology*; D004063:Digestion; D005983:Glutens / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020738:Leptin / Q000378:metabolism*; D010434:Pepsin A / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects*; D054411:Receptors, Leptin / Q000378:metabolism*; D014908:Triticum / Q000737:chemistry*; D014357:Trypsin / Q000378:metabolism
chemical_list: D004044:Dietary Proteins; D020738:Leptin; D054411:Receptors, Leptin; D005983:Glutens; D014357:Trypsin; D010434:Pepsin A