Fasting-induced activation of mitogen-activated protein kinases (ERK/p38) in the mouse hypothalamus.

Activity-dependent changes in neuronal plasticity depend critically on gene regulation. To understand how fasting-induced stimulation leads to gene regulation through intracellular signalling pathways, we investigated the effect of fasting on activation of the mitogen-activated protein kinase (MAPK) family, the extracellular signal-regulated kinase (ERK) and the p38 MAPK (p38) in mouse hypothalamus. In the hypothalamic arcuate nucleus, phosphorylation of ERK significantly increased during fasting, spatially coincident with phosphorylation of cAMP response element binding protein (CREB), induction of c-Fos, and expression of neuropeptide Y (NPY). In the paraventricular nucleus (PVN) of fasted mice, activation of p38 in addition to ERK was also observed. In the arcuate nucleus of ob/ob mice, phosphorylations of ERK and CREB were decreased during fasting, whereas the expression of NPY was increased. In the PVN, increased activation of p38 was observed in spite of decreased activation of ERK. These results suggest that ERK and p38 are differentially activated by fasting in distinct regions of the hypothalamus depending on the condition of energy balance.