title: Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment.
abstract: BACKGROUND
  Obesity research focuses essentially on gene targets associated with the obese phenotype. None of these targets have yet provided a viable drug therapy. Focusing instead on genes that are involved in energy absorption and that are associated with a "human starvation phenotype", we have identified enteropeptidase (EP), a gene associated with congenital enteropeptidase deficiency, as a novel target for obesity treatment. The advantages of this target are that the gene is expressed exclusively in the brush border of the intestine; it is peripheral and not redundant.
  
  
  RESULTS
  Potent and selective EP inhibitors were designed around a boroarginine or borolysine motif. Oral administration of these compounds to mice restricted the bioavailability of dietary energy, and in a long-term treatment it significantly diminished the rate of increase in body weight, despite ad libitum food intake. No adverse reactions of the type seen with lipase inhibitors, such as diarrhea or steatorrhea, were observed. This validates EP as a novel, druggable target for obesity treatment.
  
  
  CONCLUSIONS
  In vivo testing of novel boroarginine or borolysine-based EP inhibitors validates a novel approach to the treatment of obesity.
authors.affiliation: ObeTherapy Biotechnology, Evry, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Braud
authors.forename: Marco A
authors.initials: MA
authors.lastname: Ciufolini
authors.forename: Itzik
authors.initials: I
authors.lastname: Harosh
mesh_terms: D000284:Administration, Oral; D020816:Amino Acid Motifs; D000818:Animals; D001120:Arginine / Q000737:chemistry; D001682:Biological Availability; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004435:Eating; D004765:Enteropeptidase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005247:Feeding Behavior; D006801:Humans; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D008956:Models, Chemical; D008957:Models, Genetic; D009765:Obesity / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D013217:Starvation / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D001120:Arginine; D004765:Enteropeptidase; D008239:Lysine