UCP2 mediates ghrelin’s action on NPY/ AgRP neurons by lowering free radicals
Zane B. Andrews et al 2008 Nature vol 454 pp 846-851
The gut-derived hormone ghrelin acts on the brain by regulating neuronal activity
Ghrelin is a hormone with widespread activity. This paper links its activity with appetite control in a complex action involving fatty acids as a hypothalamic fuel and also carbohydrate and energy intake. Anti oxidant status also has a role. No doubt in time this will become clearer.
Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). The authors show that ghrelin initiates changes in hypothalamic mitochondria! respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2.
- Martin Eastwood