[Frontiers in Bioscience E2, 1355-1361, June 1, 2010]

Contribution of central SGK-1 to the acute phase responses of mice to social isolation

Takao Kaji, Katsunori Nonogaki

Department of Lifestyle Medicine, Biomedical Engineering Center, Tohoku University and Metabolic Care Clinic, Tohoku University Hospital, 1-1 Seiryou-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. Materials and methods
3.1. Experimental procedures
3.2. levels of ghrelin and cortisone in the blood chemistry
3.3. Real-time quantitative RT-PCR
3.4. Small interfering RNA (siRNA)
3.5. Data analysis
4. Results
4.1. Effects of social isolation on plasma corticosterone and ghrelin levels, and the expression of hypothalamic genes
4.2. Effects of SGK-1 siRNA oligonucleotide treatment
4.3. Effects of adrenergic receptor antagonists on acute isolation stress-reduced body weight
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

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 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.