A New Appetite Regulating Factor : (Clusterin)

다국어 초록 (Multilingual Abstract)

Food intake and energy expenditure is tightly regulated by homeostatic mechanism so as to maintain relatively constant body weight. A mismatch, even if small, between food intake and energy expenditure causes obesity or cachexia if it is accumulated for a long period. It has long been thought that the central nervous system, especially hypothalamus plays a central role in the physiologic regulation of food intake and body weight.
In the hypothalamus, leptin and insulin signaling is important for suppression of food intake and lowering body fat mass. Disruptions in these signaling systems have been shown to induce obesity-hyperphagia syndrome. Increased expression of suppresor of cytokine signaling(SOCS)-3 in the hypothalamus is associated with central leptina resistance. However, the mechanisms of impaired leptin and insulin signaling are mostly unknown.
Clusterin(apoprotein J) is the 80 kilo dalton disulfide-linked glycoprotein that is abundantly present in body fluids. Clusterin is expressed in the hypothalamus, a key organ regulating food intake and body weight. We have found that hypothalamic clusterin expression was increased by food intake but this change was blunted in high fat diet fed obese mouse, suggesting that clusterin may have a role in the control of food intake and body weight.
To investigate the role of clusterin in the hypothalamus, we administered synthetic full length secretary form of clusterin into the 3rd cerebroventricle, adjacent to the hypothalamus, of C57BL/6J mice and monitored food intake and body weight. Intracerebroventricular(ICV) administration of clusterin significantly decreased fasting-induced feeding and reduced body weight at 24 h post injection. Consistent with these findings, bilateral injection of clusterin-adenovirus in mediabasal hypothalamus decreased food intake but increased energy expenditure, resulting in decreased body weight. Similarly to leptin, ICV administration of clusterin increased Signal Transducer Activated Transcript(STAT)-3 phosphorylation in the hypothalamic neurons. Co-administration of sub-clinical dose of clusterin potentates the anorexigenic effect of leptin. Our data identify clusterin as a novel anorexigenic molecule.