Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment.
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",...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3504148?pdf=render |
| _version_ | 1819103897602490368 |
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| author | Sandrine Braud Marco A Ciufolini Itzik Harosh |
| author_facet | Sandrine Braud Marco A Ciufolini Itzik Harosh |
| author_sort | Sandrine Braud |
| collection | DOAJ |
| description | 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. |
| first_indexed | 2024-12-22T01:57:46Z |
| format | Article |
| id | doaj.art-1266ac4e4b7d4450a3fa533814443620 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T01:57:46Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1266ac4e4b7d4450a3fa5338144436202022-12-21T18:42:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4961210.1371/journal.pone.0049612Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment.Sandrine BraudMarco A CiufoliniItzik HaroshBACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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.http://europepmc.org/articles/PMC3504148?pdf=render |
| spellingShingle | Sandrine Braud Marco A Ciufolini Itzik Harosh Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. PLoS ONE |
| title | Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. |
| title_full | Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. |
| title_fullStr | Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. |
| title_full_unstemmed | Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. |
| title_short | Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment. |
| title_sort | enteropeptidase a gene associated with a starvation human phenotype and a novel target for obesity treatment |
| url | http://europepmc.org/articles/PMC3504148?pdf=render |
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