Ghrelin Stimulates Growth Hormone Secretion and Food Intake in Aged Animals

Abstract

Age-related decreases in energy expenditure have been associated with the loss of skeletal muscle and decline of food intake, possibly through a mechanism involving changes of growth hormone (GH) secretion and feeding behavior. Age-related declines of growth hormone secretion and food intake have been termed the somatopause and anorexia of ageing, respectively. Ghrelin, a 28-amino-acid peptide, was isolated from human and rat stomachs as an endogenous ligand of growth hormone secretagogue receptor. Ghrelin stimulates growth hormone release and food intake when peripherally administered to rodents and humans. PURPOSE: We investigate the relationship between age-related decline of growth hormone secretion and/or food intake and ghrelin function. METHODS: Male Long-Evans rats (4-week-old) were used. All rats were housed individually in plastic cages at constant room temperature and were given standard laboratory chow and water ad libitum. Experiments were conducted on rats at 3, 12, 24, and 27 months of age. Ghrelin (10 nmol/kg body weight) was administered intravenously to rats, after which GH concentrations and 2-hour food intake were measured. The plasma concentration of GH was determined with a Rat GH RIA kit. RESULTS: Body weight increased gradually in rats from 3- to 24-month of age. The body weight in 27-month-old rats was significantly decreased compared to 24-month-old rats. Food intake for 24 hours did not change from 3- to 24-month-old rats, while 24-hour food intake in 27-month-old rats was significantly decreased compared to 24-month-old rats. An intravenous administration of ghrelin to rats increased food intake in all generations. The amounts of ghrelin-induced food intake in 27-month-old rats were significantly decreased compared to the other generations. However, the ratio of ghrelin-induced food intake to 4-hr food intake was the same among the generations. In addition to orexigenic effect by ghrelin, intravenous administration of ghrelin elicited a marked increase in plasma GH levels, with the peak occurring 15 min after administration. CONCLUSIONS: Ghrelin replacement may improve physical abilities to stimulate GH secretion and feeding in aged animals. The present study will provide novel insights into the physiological function of ghrelin in ageing process.