Contribution of central SGK-1 to the acute phase responses of mice to social isolation.
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.
Kaji
Takao
T
Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University and Metabolic Care Clinic, Tohoku University Hospital, Sendai, Miyagi 980-8574, Japan.
Nonogaki
Katsunori
K
D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001835:Body Weight; D003348:Cortisone / Q000097:blood; D017931:DNA Primers; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000097:blood; D017874:Immediate-Early Proteins / Q000502:physiology*; D051379:Mice; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012934:Social Isolation; D000099184:Serum-Glucocorticoid Regulated Kinases
D003348:Cortisone; D017931:DNA Primers; D054439:Ghrelin; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D000099184:Serum-Glucocorticoid Regulated Kinases