Experimental Approach to Test Predictions of Body Weight Regulation Models

Background: Although body weight regulation models have been proposed, experimental approaches for testing their predictions are lacking. The set point (SP) model proposes that a biologically determined fatness is defended by activating compensatory responses to prevent its change. The dual-intervention point (DIP) model proposes that there are two levels of fatness (lower and upper intervention points) within which fatness is weakly regulated. Compensatory responses would only be activated once the lower or upper intervention points are reached. In response to prolonged fasting, the SP model predicts the compensatory responses to be independent of the initial body weight. In contrast, the DIP model predicts higher responses in individuals who are closer to the lower intervention point (low body weight) compared to those who are farther away (obesity). None of these models predicts a different response in men vs. women. Our pilot and feasibility study will implement an experimental approach to test these predictions in humans by thoroughly measuring compensatory responses in energy expenditure and energy intake. Design: Twelve individuals (3 men with low body weight and 3 with obesity; 3 women with low body weight and 3 with obesity) will be kept inpatient in metabolic chambers for 5 consecutive days and exposed to a 1-day energy balance, 2-day fasting, and 2-day ad-libitum refeeding. The primary outcome will be the extent of compensatory response, calculated as the cumulative energy balance during the 5-day inpatient period. Objectives: 1. To determine the extent of compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans overall and among different subgroups (low body weight, obesity, men, women). 2. To explore the timing of the compensatory responses during a 2-day fasting followed by a 2-day ad-libitum refeeding in humans. 3. To explore potential physiological determinants of the inter-individual variability in the compensatory response induced by a 2-day fasting followed by a 2-day ad-libitum refeeding in humans. Relevance: Understanding how body weight is regulated in humans can help to prevent or treat obesity. In this pilot and feasibility study, the investigators propose an experimental approach to test the predictions of two body weight regulation models in response to fasting and explore potential sex differences. These preliminary data will be used to design and power future studies for testing models of body weight regulation in humans.