Ghrelin, Obestatin, and Nesfatin - NEWLY UPDATED!

Growth hormone releasing peptide 6 (GHRP-6) was the first synthetic peptide that was shown to release growth hormone (GH) and stimulate weight gain by binding to growth hormone secretagogue receptor type 1a (GSR1a). Ghrelin, the endogenous ligand for GSR1a, was later isolated. This orexigenic and GH releasing peptide is derived from ghrelin preproprotein. It is expressed primarily in the stomach and has been shown to decrease insulin levels and increase appetite, body weight gain, fat accumulation, and glucose and GH levels, suggesting this peptide plays a highly important physiological role in metabolism. In addition, it may also modulate cell proliferation of cancer cells and cardiomyocytes.

Two forms of ghrelin can be found in circulation: an acylated form and a non-acylated form. The acylated form of ghrelin contains an n-octanoic acid at the Ser3 residue that is required for activation of GSR1a. Therefore, it was originally believed that des-acyl ghrelin, which lacks this esterification at Ser3, is an inactive form though it is the predominant one found in circulation. Accumulating evidence, however, indicates that des-acyl ghrelin can counteract some metabolic responses of acylated ghrelin in humans, and mice injected with or over expressed with the des-acyl form were found to decrease food in- take and gastric emptying. Other studies showed both forms of ghrelin mediate cell proliferation and fat accumulation. Collectively, these studies suggest an alternative receptor exists for ghrelin that is not dependent on n-octanoylation of Ser3 for activation. Studying des-acyl ghrelin may offer new insight into the regulation of homeostasis and energy balance.

Currently, in addition to ghrelin, a number of gastrointestinal hormones have been identified that control appetite by either stimulating food intake and gastric emptying or inhibiting these responses. Zhang et al. has recently identified one of the newest members of this family by using bioinformatic predictions about enzyme cleavage of the prepropeptide of ghrelin. The newly identified 23 amino acid, ghrelin-associated peptide was named obestatin (PGH-3890-PI and PGH-3891-PI). Though both peptides originate from the same precursor prepropeptide, they have opposing physiological roles.

Peptides International offers the recently discovered obestatin, truncated obestatin, full length acyl and des-acyl ghrelin and ghrelin fragments, and several ghrelin antagonists to complete your research needs. Our acyl and des-acyl ghrelin fragments consisting of the first 5, 10, 14 or 18 amino acids and contain the core amino acids required for proper binding and activation of GHSR1a.13 [Dap3]-Ghrelin (Rat) (PGH-3680-PI) and [Dap3]-Ghrelin (Human, Rat, 1-5) (PGH-3681-PI) analogs are replaced with 2,3-diaminopropionic acid (Dap) at Ser3. This substitution should make the analogs more stable and less susceptible to esterases and acyl migration. Ghrelin analogs with the Dap substitution have been shown to activate growth hormone secretagogues receptor 1a (GH- SR1a) just as efficiently as the parent peptide. The variety of research tools we are able to offer at Peptides International may help scientists elucidate the complex regulation of appetite and weight gain.

Authors from Peptides International

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