Endocrine Abstracts

Binding of the gastric hormone ghrelin to its cognate receptor, GHS-R_1a, is dependent upon the acylation of its third (serine) residue. Although acute exposure to ghrelin stimulates the secretion of growth hormone (a potent lipolytic signal), chronic exposure to ghrelin promotes fat deposition¹.

We have shown that in intra-abdominal depots, ghrelin-induced fat accumulation is depot-specific, time-dependent, due to lipid accumulation resulting from suppressed lipolysis and is probably mediated by GHS-R_1a in adipocytes^2,3. Like other G protein-coupled receptors (CPCRs), it is becoming evident that activation of GHS-R_1a may be modulated by heterodimerization with other GPCR species and by regulation of intracellular signalling components⁴. These processes may underlie the depot-specific sensitivity of adipose tissue to ghrelin.

Although inguinal fat (a deep subcutaneous depot) exhibits many of these ghrelin-induced responses, superficial subcutaneous adipose tissue is unaffected by exposure to ghrelin^2,3. In bone marrow, however, ghrelin increases adiposity by a direct induction of adipogenesis. This increase in adipocyte number is unlikely to be mediated by GHS-R_1a, since it is also induced by unacylated ghrelin but not by the GHS-R_1a-specific ligand L163 255².

In physiological terms, continuous exposure to elevated circulating ghrelin, which signifies prolonged nutritional insufficiency, appears to exert depot-specific gating of lipid utilization, whilst ghrelin and UAG promote the accumulation of adipocytes in bone marrow by an unknown receptor.

References

1. Tschöp M et al. 2000 Nature 407 908–913.

2. Thompson NM et al. 2004 Endocrinology 145 234–242.

3. Davies JS et al. 2007 Proceedings of the 89th Annual Meeting of the Endocrine Society Ab P1–31.

4. Davies JS et al. 2006 Proceedings of the 88th Annual Meeting of the Endocrine Society Ab P3–118.