REVIEW Shedding light on the intricate puzzle of ghrelin’s effects on appetite regulation

Ghrelin, a hormone primarily produced by the stomach, has a wide range of metabolic and non-metabolic effects. It also stimulates food intake through activation of various hypothalamic and brain stem neurons. A series of recent studies have explored the intracellular mechanisms of the appetite-inducing effect of ghrelin in the hypothalamus, shedding light on the intricate mechanisms of appetite regulation. AMP-activated protein kinase (AMPK) is a key metabolic enzyme involved in appetite regulation. Calmodulin kinase kinase 2 (CaMKK2) has been identified as an upstream kinase of AMPK and a key mediator in the effect of ghrelin on AMPK activity. The fatty acid pathway, hypothalamic mitochondrial respiration, and uncoupling protein 2 have been outlined as downstream targets of AMPK and mediators of ghrelin’s appetite stimulating effect. This short overview summarises the present data in this field. Journal of Endocrinology (2009) 202, 191–198 of food intake. In this figure, we have a simplified, linear relationship among the elements comprising the ghrelin signalling cascade. Clearly, the different components of this cascade can also interact within and outside this pathway, activating other distinct downstream signalling components, here not reported, either sequentially or simultaneously, suggesting a much more complex regulation. This figure has been drawn based on the studies of Andersson et al . (2004), Landree et al . (2004), Kola et al . (2005, 2008), Anderson et al . (2008), Andrews et al . (2008) and Lopez et al . (2008). GHSR, GH secretagogue receptor; CaMKK, calmodulin kinase kinase; CB1, cannabinoid receptor type 1; AMP-activated protein acetyl-coenzyme A carboxylase; malonyl-CoA, malonyl coenzyme acid synthase; palmitoyl transferase

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