Shades of Ghrelin in Weight Homeostasis

Thu, 06/14/2012 - 16:48

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

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