Ghrelin is directly involved with short-term regulation of energy balance. Although circulating levels of ghrelin are elevated in anorexia nervosa and reduced in obesity, the role of ghrelin in regulating long-term energy balance in healthy women has not been investigated. We examined the effects of a 3-month energy deficit-imposing diet and exercise intervention on circulating ghrelin in normal-weight, healthy women. Body composition, resting metabolic rate, and serum ghrelin were measured at pre-, mid-, and postintervention in controls (n = 7), who performed no exercise, and exercising women who remained weight stable (n = 5) or lost weight (n = 10). Exercise training occurred five times per week, and subjects were fed a specific diet. Ghrelin significantly increased over time (770 +/- 296 to 1322 +/- 664 pmol/liter) in the weight-loss group compared with the controls and the weight-stable group (P < 0.05). Changes in ghrelin were negatively correlated with changes in body weight (r = -0.61; P < 0.05). Body fat, body weight, and resting metabolic rate significantly decreased in the weight-loss group before the increase in ghrelin. These findings suggest that ghrelin responds in a compensatory manner to changes in energy homeostasis in healthy young women, and that ghrelin exhibits particular sensitivity to changes in body weight.

LEIDY, HEATHER J., KELLY A. DOUGHERTY, BRIAN R. FRYE, KRISTIN M. DUKE, AND NANCY I. WILLIAMS. Twenty-four-hour ghrelin is elevated after calorie restriction and exercise training in non-obese women. Obesity. 2007;15:446 -455. Objective: The purpose of this study was to determine whether chronic energy deficiency achieved with caloric restriction combined with exercise is associated with changes in the 24-hour profile of ghrelin in non-obese, pre-menopausal women. Research Methods and Procedures:Twelve non-obese (BMI ϭ 18 to 25 kg/m 2 ), non-exercising women (age, 18 to 24 years) were randomly assigned to a non-exercising control group or a diet and exercise group. The 3-month diet and exercise intervention yielded a daily energy deficit of Ϫ45.7 Ϯ 12.4%. Serial measurements were made of body composition, energy balance, and feelings of fullness. Repeated blood sampling over 24 hours to measure ghrelin occurred before and after the study. Results: Significant decreases in body weight, body fat, and feelings of fullness were observed in only the energy-deficit group (p Ͻ 0.05); significant changes in the following ghrelin features were found in only the deficit group (p Ͻ 0.05): elevations in baseline (ϩ353 Ϯ 118 pg/mL), lunch peak (ϩ370 Ϯ 102 pg/mL), dinner peak (ϩ438 Ϯ 149 pg/mL), nocturnal rise (ϩ269 Ϯ 77 pg/mL), and nocturnal peak (ϩ510 Ϯ 143 pg/mL). In addition, we found a larger dinner decline (Ϫ197 Ϯ 52 pg/mL) and negative correlations between changes in the ghrelin dinner profile and changes in body weight (R ϭ 0.784), 24-hour intake (R ϭ 0.67), energy deficiency (R ϭ 0.762), and feelings of fullness (R ϭ 0.648; p Ͻ 0.05). Discussion: Changes in ghrelin concentrations across the day after weight loss are closely associated with other physiological adaptations to energy deficiency, further supporting the role of ghrelin as a countermeasure to restore energy balance.

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