Ghrelin is a hormone produced mainly by P/D1 cells which line the fundus of the stomach and epsilon cells of the pancreas that stimulate hunger. Ghrelin exists in an endocrinologicaly inactive (des-acyl ghrelin) and active (n-octanoyl-modified ghrelin) forms. The serum- and glucocorticoid-inducible kinase 1 (SGK-1) is a member of the AGC family of serine/threonine protein kinase. In this study, mice were isolated individually or in groups, and deprived from food supply for a period of 24-h. Despite decreases in plasma corticosterone levels and no changes in plasma des-acyl ghrelin, and the expression of hypothalamic neuropeptide Y and proopiomelanocortin, plasma active ghrelin levels and the expression of hypothalamic SGK-1 were increased in the acute-isolated mice. Injection of SGK-1 small interfering RNA (siRNA) oligonucleotide into the third cerebral ventricle suppressed the acute social isolation-induced decreases in body weight and increases in plasma active ghrelin levels. Pretreatment with phentolamine (alpha-adrenergic receptor antagonist) but not alprenolol (beta-adrenergic receptor antagonist), partially but significantly suppressed the decreases in body weight induced by acute isolation stress. These finding suggest that isolation stress is a novel inducer of hypothalamic SGK-1 expression. SGK-1 might contribute to the isolation stress-induced body weight reductions and increases in plasma active ghrelin levels via, at least partly, altered central autonomic outflow in mice.