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Gut hormones as peripheral anti obesity targets.
- Source :
-
Current drug targets. CNS and neurological disorders [Curr Drug Targets CNS Neurol Disord] 2004 Oct; Vol. 3 (5), pp. 379-88. - Publication Year :
- 2004
-
Abstract
- Many peptides are synthesised and released from the gastrointestinal tract. Whilst their roles in regulation of gastrointestinal function have been known for some time, it is now evident that they also influence eating behaviour and thus potential anti obesity targets. Peptide YY (PYY) is released post prandially from the gastrointestinal L-cells with glucagon-like peptide 1 (GLP-1) and oxyntomodulin. Following peripheral administration of PYY 3-36, the circulating form of PYY, to mouse, rat or human there is marked inhibition of food intake. PYY 3-36 is thought to mediate its actions through the NPY Y2 GPCR. Obese subjects have lower basal fasting PYY levels and have a smaller post prandial rise. However, obesity does not appear to be associated with resistance to PYY (as it is with leptin) and exogenous infusion of PYY 3-36 results in a reduction in food intake by 30% in an obese group and 31% in a lean group. GLP-1 or oxyntomodulin, products of the prepreglucagon gene, decrease food intake when administered either peripherally or directly into the CNS. In addition, both have been shown to decrease food intake in humans. These effects are thought to be mediated by the GLP-1 receptor. Ghrelin, a huger hormone produced by the stomach, increases in the circulation following a period of fasting. Administration of ghrelin either peripherally or directly into the CNS increases food intake and chronic administration leads to obesity. Further infusion into normal healthy volunteers increases both food intake and appetite. Ghrelin is thought to act through the growth hormone secretagogue receptor (GHS-R). Obesity is the current major cause of premature death in the UK, killing almost 1000 people a week. Worldwide its prevalence is accelerating. The administration of the naturally occurring gut hormone may offer a long-term therapeutic approach to weight control. Here we consider the therapeutic potential of some gut hormones, and the GPCR's through which they act, in the treatment of obesity.
- Subjects :
- Animals
Anti-Obesity Agents pharmacology
Anti-Obesity Agents therapeutic use
Appetite Regulation drug effects
Drug Design
Gastrointestinal Hormones agonists
Gastrointestinal Hormones antagonists & inhibitors
Ghrelin
Glucagon drug effects
Glucagon metabolism
Glucagon-Like Peptide 1
Glucagon-Like Peptides drug effects
Glucagon-Like Peptides metabolism
Humans
Mice
Obesity drug therapy
Oxyntomodulin
Pancreatic Polypeptide drug effects
Pancreatic Polypeptide metabolism
Peptide Fragments drug effects
Peptide Fragments metabolism
Peptide Hormones drug effects
Peptide Hormones metabolism
Peptide YY drug effects
Peptide YY metabolism
Protein Precursors drug effects
Protein Precursors metabolism
Rats
Receptors, G-Protein-Coupled drug effects
Anti-Obesity Agents classification
Appetite Regulation physiology
Gastrointestinal Hormones metabolism
Obesity metabolism
Receptors, G-Protein-Coupled metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1568-007X
- Volume :
- 3
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Current drug targets. CNS and neurological disorders
- Publication Type :
- Academic Journal
- Accession number :
- 15544446
- Full Text :
- https://doi.org/10.2174/1568007043336950