Abstract

Ghrelin and peptide YY (PYY) are appetite related hormones which may influence energy balance. In anorexia nervosa, a model of severe energy deficiency, ghrelin and PYY remain elevated after consuming a standardized meal and may be related to the etiology of the disorder. Amenorrhea in exercising women is associated with significant but less severe energy deficiency. Whether alterations in gut hormone responses to a single meal contribute to energy deficiency in this population is unclear. The purpose of this investigation was to compare the postprandial response of PYY and ghrelin to a mixed meal in amenorrheic (AMEN n=7) and eumenorrheic (EUMEN n=9) exercising women. Menstrual status was assessed by self report history of menses and confirmed by daily urinary measures of estrogen and progesterone metabolites. Serial blood draws and subjective appetite measures were obtained before consuming a 700kcal standardized mixed composition meal (14% PRO, 64% CHO, 22% FAT) and at regular intervals until 180 minutes post. PYY (3-36) and total ghrelin were assayed in serum by RIA. Baseline Total T3 was assessed by Immulite. Statistical analyses included independent t-tests, two-way repeated measures ANOVA (LSD post-hoc), and correlations. Subjects were similar in age (23±1 yrs), height (168±2 cm), and weight (61.0±1.6 kg). AMEN had lower Total T3 at baseline compared to EUMEN (55.3±3.7, 76.1±4.8, p=0.01). PYY increased from pre (29.8±3.9 pmol/L) to 15min post (34.1±4.1 pmol/L) (time; p<0.001) and remained elevated through 180 minutes. Change in ghrelin depended on group (time*group; p=0.02), such that ghrelin was significantly greater in AMEN than EUMEN (2810.1±456.4 pg/mL, 1511.2±138.9 pg/mL; p=0.03) prior to the meal and both absolute (1709.7±352.2 pg/mL, 593.8±125.3 pg/mL, p=0.02) and percent decrease (55.8 ±5.9%, 36.6±4.7%, p=0.02) in ghrelin from PRE to nadir were significantly greater in AMEN than EUMEN. AUC for change from baseline through 180 min was significantly greater in AMEN than EUMEN (14941.8±2455.4, 4675.2±1089.1, p=0.001) for ghrelin but did not differ for PYY (130.7±29.7, 108.4±36.3, p=0.67). There were no differences in subjective appetite scores of hunger and satiety between groups and change in appetite score was not correlated with baseline ghrelin or PYY. Baseline ghrelin was highly correlated with nadir (r=0.81, p<0.001) and AUC (r=.86, p<0.001). These results suggest ghrelin, an orexigenic hormone, is elevated in conditions of energy deficiency which may be an adaptive response to increase energy intake and reverse the underlying energy deficit. The greater magnitude of ghrelin suppression following meal consumption in amenorrheic women may be related to the elevated baseline concentration. Future studies should explore if the greater meal related decline in ghrelin is related to reduced food intake or increased satiety. Childhood Obesity Prevention Training grant.

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