Obestatins

Introduction

Obestatin is a 23 amino-acid amidated peptide and produced in specialized epithelial cells of the stomach. It can coexist with ghrelin around the islets. Obestatin was originally identified as an anorectic peptide. Therefore, it was initially reported that obestatin reduces food intake, body weight gain, and gastric emptying and to suppress intestinal motility by interaction with the orphan receptor G protein-coupled receptor 39 (GPR39). Obestatin is found in various tissues, including the stomach and has the opposite effect on ghrelin in food intake. In addition, it plays a role in energy balance. However, obestatin opposes the function of ghrelin that is growth hormone secretion and increased appetite.

Mechanism of action

Recently obestatin has been reported to regulate glucose-induced insulin secretion in perfused rat pancreatic islets. A particularly surprising report is that obestatin can bind to and activate the receptor of glucagon-like peptide-1 (GLP-1) that is an incretin hormone released from the L-cells of the small intestine. However, obestatin modulates glucose-induced insulin secretion at the level of the islet, unlike GLP-1 it neither stimulates the insulin secretion response nor causes a decrease in plasma glucose when injected into mice. Interestingly, obestatin has been shown to up-regulate the gene expression of insulin and the GLP-1 receptor in pancreatic islets.

Application of Obestatin

Some studies have shown that obestatin reduces food and water intake, reduces weight gain, inhibits gastrointestinal motility, and regulates glucose-induced insulin secretion. For example, intraperitoneal injection of obestatin inhibits food intake in a time- and dose-dependent manner. Furthermore, obestatin has recently been reported to regulate glucose-induced insulin secretion in perfused rat islets. Parallel changes in obestatin in the blood circulation provide another clue to the physiological function of obestatin in regulating appetite and metabolism. There is some data showing that in young adult male rats, the newly discovered obestatin can inhibit feeding, but does not alter the growth hormone and corticosterone release in young rats.

References

1. Subasinghage, A. P., Green, B. D., Flatt, P. R., Irwin, N., & Hewage, C. M. (2010). Metabolic and structural properties of human obestatin {1–23} and two fragment peptides. Peptides, 31(9), 1697-1705.
2. Gourcerol, G., St-Pierre, D. H., & Tache, Y. (2007). Lack of obestatin effects on food intake: should obestatin be renamed ghrelin-associated peptide (GAP)?. Regulatory peptides, 141(1-3), 1-7.