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Posts Tagged ‘Ghrelin antibody’

Ghrelin: Targeting the Hunger Hormone to Combat Obesity and Type 2 Diabetes

Wednesday, February 20th, 2013

As the hormone ghrelin is linked to appetite and weight gain, as well as impaired glucose-induced insulin secretion, there is considerable interest in this peptide as a potential drug target. Although the overall lack of success in this field has been disappointing, research inhibiting the ghrelin-modifying enzyme GOAT (MBOAT4) has produced promising results.

Ghrelin is a peptide hormone secreted by the stomach. Though first described as the ligand of the growth hormone secretagogue receptor, ghrelin has gained notoriety since it was found that circulating ghrelin levels rise then fall before and after a meal respectively, and that it stimulates appetite and weight gain. Targeting the ghrelin system could therefore be a way to treat or prevent obesity. Obese people actually have low circulating ghrelin, but it has been shown that in these individuals the suppression of ghrelin after eating is much less, suggesting that inhibiting the ghrelin system could still be an effective way to lessen appetite in the obese. Additionally, ghrelin is expressed in the pancreas, and studies have associated ghrelin with reduced glucose tolerance; thus, antagonism of the ghrelin system is a potential strategy for diabetes therapy.

Immunoperoxidase of monoclonal antibody to GHRL

Ghrelin is very unusual in two ways: its orexigenic effect, and its O-acylation with the eight-carbon fatty acid octanoate. This posttranslational modification at serine-3 of ghrelin is vital for it to bind to and activate its receptor. The ghrelin O-acyltransferase, abbreviated GOAT, was first identified and characterized by Yang et al. After utilizing western blotting (immunoblotting) with a ghrelin antibody to find cell lines capable of cleaving the ghrelin peptide from its precursor prepro-ghrelin, they carried out a number of experiments employing reverse-phase chromatography (to separate octanoylated and desacyl-ghrelin by their differing hydrophobicities) followed by probing with the ghrelin antibody in western blots. In this way they showed, for example, that in cells transfected with GOAT cDNA (but not other similar enzymes), ghrelin is acylated; that the conserved hydroxyl group at position 3 (serine or threonine) of ghrelin is vital for this modification; and that the GOAT catalytic residues are the conserved asparagine and histidine.

Blocking GOAT from acylating ghrelin could be a way to prevent its effects. Barnett et al. have obtained some encouraging results with the novel compound GO-CoA-Tat. This bisubstrate analog comprises a (partial) octanoylated ghrelin, CoA (the acyl donor), and a Tat peptide to aid cell penetration. They demonstrated in cell lines that GO-CoA-Tat inhibits ghrelin acylation by GOAT, is a selective antagonist for this enzyme and is nontoxic. They then administered GO-CoA-Tat to mice and found that again the drug was nontoxic and acyl ghrelin levels decreased; furthermore, when fed a high-fat diet, mice treated with GO-CoA-Tat were protected from the weight gain seen in untreated controls, and exhibited lower fat mass. Moreover, following a glucose challenge, the mice treated with GO-CoA-Tat were shown to have a significantly increased insulin response and decreased blood glucose levels. Double immunohistochemical staining (IHC) of pancreatic islets from the mice with insulin and ghrelin antibodies revealed ghrelin-producing cells (ghrelin-positive and insulin-negative) in addition to the beta cells. Together, these findings indicate that GOAT inhibition may be a useful treatment strategy for both obesity and type 2 diabetes. This is particularly significant because of the lack of success achieved by groups using other approaches (neutralizing ghrelin in circulation, or antagonising ghrelin’s receptor GHS-R1a).

  1. PMID: 21835215
  2. PMID: 18267071
  3. PMID: 21097901

Written by Carly Hammond

Shades of Ghrelin in Weight Homeostasis

Thursday, June 14th, 2012

The neuropeptide and gut hormone Ghrelin is an endogenous ligand for the growth hormone (GH)-secretagogue receptor (GHSR) within the central nervous system. This pathway has received a great deal of attention and heavy study within the last decade because of its large role in numerous physiological processes including feeding and body weight homeostasis (1, 2). In particular, Ghrelin is a key regulator of reward-based eating behavior (2, 3). Specifically, Ghrelin is derived from preproghrelin, which also generates another peptide called obestatin.

Immunoperoxidase of monoclonal antibody to GHRL

Obestatin is an endogenous ligand for the orphan G protein-coupled receptor GPR39 and is involved in satiety and decreased food intake. Clinical trials have already been done to determine if Ghrelin can be used in the treatment of disorders such as anorexia, cachexia, and GH-related conditions1. Exact distribution of ghrelin in the CNS is unclear as published results are inconsistent. The use of several Ghrelin antibodies by Furness et al showed only insignificant amounts of authentic ghrelin in the CNS (4). Yet Kedzia, et al. showed that Ghrelin expression can be found in the glandular pituitary and CNS in human fetal tissue when using Ghrelin antibodies (5). A study pairing RT-PCR mRNA expression with Ghrelin antibody immunohistochemistry also detected Ghrelin peptide expression in a variety of reproductive and endocrine organs, GI organs, and neural tissues such as pituitary, adrenal gland, and spinal cord (6). Further work needs to be done to untangle this inconsistent distribution and expression data. Some recent studies using Ghrelin antibody to attenuate the oreixgenic effects of food deprivation on energy metabolism/food intake suggests that an oligoclonal approach of antagonizing endogenous Ghrelin may be worth pursuing (7). Interestingly, preliminary studies using breast cancer specimens hint that Ghrelin antibody immunostaining, along with that of Obestatin, might serve as prognostic biomarkers8.

  1. PMID: 22385874
  2. PMID: 21524673
  3. PMID: 22458951
  4. PMID: 21835225
  5. PMID: 20164039
  6. PMID: 19670151
  7. PMID: 22149064

Novus Biologicals offers ghrelin reagents for your research needs including:

Appetite and Energy: A Ghrelin Balancing Act

Thursday, May 17th, 2012

Ghrelin is the only potent orexigenic peptide in circulation. It stimulates food intake and leads to metabolism regulation, positive energy balance, adipogenesis, and body weight gain. However, in studies using ghrelin antibodies, the physiological significance of ghrelin in the regulation of energy homeostasis is controversial, since loss of ghrelin function in rodents does not necessarily lead to anorexia and weight loss (1). Research using ghrelin antibodies shows that ghrelin is a brain-gut circuit peptide with an important role in the physiological regulation of appetite, response to hunger and starvation, metabolic and endocrine functions as energy expenditure, gastric motility and acid secretion, insulin secretion and glucose homeostasis, as well as in the potential connection to the central nervous system (2).

Immunoperoxidase of monoclonal antibody to GHRL

Immunoperoxidase of monoclonal antibody to GHRL

Besides its functions in regulating energy homeostasis, ghrelin has pronounced cardioprotective effects and was shown to improve cardiac performance in chronic heart failure (CHF).  Studies using ghrelin antibodies suggest that the multifunctional nature of ghrelin makes it an interesting pharmacological target for various diseases. Additional ghrelin antibody-based studies show that inhibition of ghrelin could be a promising approach in obesity-related disorders, while an enhancement of the ghrelin response is considered beneficial in several pathologic conditions marked by malnutrition, wasting and cachexia, including CHF, cancer, chronic pulmonary disease or chronic infections (3).

  1. PMID: 22249814
  2. PMID: 22041110
  3. PMID: 22074572

Novus Biologicals offers ghrelin reagents for your research needs including: