Altered Appetite-Mediating Hormone Concentrations Precede Compensatory Overeating After Severe, Short-Term Energy Deprivation in Healthy Adults1-5

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Adaptive responses of appetite-mediating hormones to negative energy balance are thought to contribute to a counterregulatory response that drives weight regain, but they have not been studied while controlling for reduced diet volume.


In this secondary analysis, we aimed to determine the effects of short-term, severe energy deprivation (ED) on appetite and appetite-mediating hormone concentrations.


Twenty-one adults with a mean ± SD age of 21 ± 3 y and body mass index of 25 ± 3 kg/m2 consumed isovolumetric diets provided over separate 48-h periods while increasing habitual energy expenditure by 1683 ± 329 kcal/d through light- and moderate-intensity exercise. Energy intake was matched to energy expenditure to maintain energy balance (EB) (-44 ± 92 kcal/d) or was <10% of energy expenditure to generate a -3696 ± 742-kcal/d energy deficit. Postprandial appetite, glucose, insulin, acyl ghrelin, peptide YY, pancreatic polypeptide (PP), and glucagon-like peptide-1 (GLP-1) responses and ad libitum energy intake were measured as secondary outcomes after both experimental periods.


Fasting insulin (-56% ± 42%) and acyl ghrelin (-60% ± 17%) concentrations decreased during ED but not during EB (condition-by-time interaction; P-interaction ≤ 0.01), whereas fasting leptin concentrations decreased more during ED compared with during EB (-47% ± 27% compared with -20% ± 27%; P-interaction = 0.05). Postprandial insulin (57% ± 63%; P < 0.001), GLP-1 (14% ± 28%; P = 0.04), and PP (54% ± 52%; P < 0.001) areas under the curve (AUCs) were higher, whereas the acyl ghrelin AUC was lower (-56% ± 13%; P < 0.001) after ED compared with after EB. After ED, self-rated appetite was greater, and ad libitum energy intake was 811 kcal/36 h (95% CI: 184, 1439 kcal/36 h) higher relative to after EB (P = 0.01).


Short-term, severe ED suppressed acyl ghrelin concentrations and increased postprandial anorexigenic hormone concentrations. These effects preceded compensatory overeating, suggesting that in adults without obesity, altered sensitivity to appetite-mediating hormones may contribute to an adaptive counterregulatory response during the initial stages of negative EB. This trial was registered at as NCT01603550. J Nutr 2016;146:209-17.

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