Abstract
There are several lines of evidence suggesting that the AMP-activated protein kinase (AMPK) signaling pathways in the hypothalamus are involved in the regulation of energy balance. The phosphorylation of AMPK increased in the hypothalamus under the fasted condition, and the constitutive-active AMPK reportedly increased food intake and body weight. Furthermore, several peripheral signals related to energy balance are shown to affect the AMPK signaling in the hypothalamus. On the other hand, we reported previously that ghrelin and insulin, representative orexigenic and anorexigenic hormones, respectively, affected neuropeptide Y (NPY) gene expression in the arcuate nucleus only in the presence of glucocorticoids, suggesting that glucocorticoids play a permissive role in the regulation of NPY gene expression. To elucidate the relationship between glucocorticoids and AMPK signaling, we examined the effects of glucocorticoids on the expression of NPY and agouti-related peptide (AGRP) as well as phosphorylated AMPK (p-AMPK) in the hypothalamic organotypic cultures. The incubation with dexamesasone (DEX) increased the expression levels of p-AMPK in the explants, accompanied by significant increases in NPY and AGRP gene expression in the arcuate nucleus. The addition of compound C to the medium, which blocked the increase in the expression of p-AMPK by DEX, significantly attenuated NPY and AGRP expression stimulated by DEX. These data suggest that the AMPK signaling pathway is downstream of glucocorticoids to increased NPY and AGRP gene expression in the arcuate nucleus. [J Physiol Sci. 2008;58 Suppl:S43]
