MATADOR: Minimising Adaptive Thermogenesis And Deactivating Obesity Rebound

INTERVENTION: The study will comprise 3 phases: [1] Baseline energy balance, [2] Energy restriction intervention, and [3] Post‐intervention energy balance. As we have previously shown that provision of food maximises dietary compliance in the free‐living situation (1,2,4), food will be home‐delivered weekly to participants in all phases of this study. The aim of PHASE 1 is to determine the baseline values of various parameters of the famine reaction before energy restriction and weight loss. During the 4 weeks of PHASE 1, weight stability will be achieved as we have previously published (1‐4), by determining maintenance energy requirements from dietary history and resting metabolic rate (RMR), and then providing participants with a weight maintenance diet. In PHASE 2, participants will be randomised to continuous or intermittent energy restriction interventions. The continuous intervention consists of 16 weeks on a diet at 67% of maintenance energy requirements. The intermittent intervention consists of 16 weeks of total energy restriction administered as 2 weeks of energy restriction on a diet at 67% of maintenance energy requirements followed by 2 weeks of energy balance on a diet at 100% of maintenance energy requirements, for a total of 30 weeks. The interventions are designed to elicit a 10% body weight loss. To account for weight lost, the energy restriction will be indexed to body weight and RMR after every 4 weeks of energy restriction, thereby keeping theoretical relative energy deficit consistent across the 16‐week period. In PHASE 3, participants will be placed on an energy balance diet referenced to their reduced‐weight state for 4 weeks to examine the time course of recovery of metabolic and neuroendocrine markers. The macronutrient distribution in both energy restriction and energy balance diets will be maintained within the range of 25–30% of energy as fat, 15‐20% as protein, and 50–60% as carbohydrate. As we have previously shown that provision of food maximises dietary compliance in the free‐living situation (1,2,4), food will be home‐delivered weekly to participants in this study. 1. Weinsier RL, Hunter GR, Desmond RA, Byrne NM, Zuckerman PA, Darnell BE. Free‐living activity energy expenditure in women successful and unsuccessful at maintaining a normal body weight. Am J Clin Nutr. 2002; 75(3):499‐504. 2. Byrne NM, Hills AP, Wood RE. Does body composition, relative energy deficit or adaptive thermogenesis explain differences between predicted and actual weight loss in obese adults? Obesity Reviews. 2010;11(Suppl.1):35‐36. 3. Byrne NM, Weinsier RL, Hunter GR, et al. Influence of distribution of lean body mass on resting metabolic rate after weight loss and weight regain: comparison of responses in white and black women. Am J Clin Nutr. 2003;77(6):1368‐73. 4. Wood RE, Byrne NM, Groves AM, Hills AP, King NK. Achieving energy balance in apparently sedentary obese males. Obesity Reviews. 2010;11(Suppl.1):219. CONDITION: Obesity PRIMARY OUTCOME: Body weight will be measured using digital weighing scales. Digital weighing scales are to be used to monitor body weight of participants at home in times between laboratory visits. These scales will be calibrated regularly, and weight will also be measured at the standard laboratory sessions. Neuroendocrine status: Overnight fasted blood samples will be collected and concentrations of the following analytes in serum or plasma will be determined: free T3, Free T4, reverse T3, TSH, ACTH, cortisol, testosterone, sex hormone binding globulin, IGF‐1, and leptin. Resting metabolic rate via indirect calorimetry INCLUSION CRITERIA: Sedentary (< 60 mins physical activity per week) Class I or II obese (30‐40kg.m‐2) Waist circumference >102 cm Euthyroid, non‐diabetic, ambulatory, and weight stable for at least 6 months (+/‐2kg) SECONDARY OUTCOME: Body composition (Fat Mass and Fat‐free Mass) will be assessed using the gold‐standard 4‐compartment model using air displacement plethysmography (via BodPod), deuterium dilution and Dual Energy X‐ray Absorptiometry (DXA) at 4 time points: in energy balance immediately prior to (Phase 1), midway and immediately after the weight loss intervention (Phase 2) and after the 4‐wk period of energy balance (Phase 3). In addition, BodPod measurements will be taken at week 1 energy balance (pre‐intervention), weeks 4 and 12 of energy restriction, and weeks 1 and 2 of energy balance (post‐intervention). Fasting substrate oxidation via indriect calorimetry Markers of metabolic health (fasting serum glucose, insulin, triglycerides, cholesterol)