Obesity implies a failure of auto-regulatory homeostatic responses to caloric excess. We studied the mechanisms, effectiveness and limits of such responses in 6 lean (21.9±1.3 kg/m²), healthy men based in a metabolic suite for 17 weeks progressive intermittent overfeeding (OF) (3wk baseline, 3wk 20%OF, 1wk ad lib, 3wk 40%OF, 1wk ad lib, 3wk 60%OF, 3wk ad lib). Body composition was assessed by 4-compartment model using dual X-ray absorptiometry, deuterium dilution and plethysmography. Magnetic resonance imaging assessed subcutaneous/visceral fat at abdominal level at baseline and end of 60%OF. Energy intake was assessed throughout, energy expenditure (calEE) and substrate oxidation rates were measured by whole body calorimetry, and free-living energy expenditure (TEE) by doubly labelled water (DLW) at baseline and after 60%OF. At the end of 60%OF, calEE and TEE had increased by 11.4 (p=0.001) and 16.2% (p=0.001), respectively. Weight and body fat (FM) had increased by 5.98kg (8.8%, p=0.001) and 3.31kg (22.6%, p=0.01). The relative increase in visceral fat (32.6%, p=0.02) exceeded subcutaneous fat (13.3%, p=0.002) in the abdominal region. The computed energy cost of tissue accretion differed from the excess ingested by only 13.1% (using calEE) and 11.6% (using TEE) indicating an absence of effective dissipative mechanisms. We conclude that elevations in energy expenditure provide very limited auto-regulatory capacity in body weight regulation, and that regulation must be dominated by hypothalamic modulation of energy intake. This result supports current conclusions from genetic studies in which all known causes of human obesity are related to defects in the regulation of appetite.