Research: GONG and COLLEAGUES,

Listed in Issue 237

Abstract

GONG and COLLEAGUES,  (1)Area of Regulatory Biology, Division of Life Science, Graduate School of Science and Engineering, Saitama University, Shimo-ohkubo, Sakuraku, Saitama, Japan studied the control of ghrelin secretion and its interaction with long-chain fatty acids at the molecular level.

Background

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood.

Methodology

Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120).

Results

Addition of GW-9508 (a GPR120 chemical agonist) and α-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ∼50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pre-treatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice.

Conclusion

These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells.

References

Gong Z(1), Yoshimura M, Aizawa S, Kurotani R, Zigman JM, Sakai T, Sakata I. G protein-coupled receptor 120 signalling regulates ghrelin secretion in vivo and  in vitro.  Am J Physiol Endocrinol Metab. 306(1):E28-35. doi: 10.1152/ajpendo.00306.2013. Jan 1 2014. Epub Nov 12 2013.

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