Energy exists as organic molecules and heat in living organisms. In adult mammals, body weight and fat content remain unchanged if energy intake is strictly equivalent to energy expenditure. In other words, regulation of body weight requires energy of foods to be entirely dissipated as heat. Imbalance between ingested energy and thermogenesis induces obesity or thinness. Alterations of food intake or energy expenditure represent the two causes of body weight disturbance. It is accepted that individuals differ in food efficiency i.e. ability to metabolize foods and store fat or totally burn nutrients. Mechanisms of food efficiency and futile cycles are presented. I started my research work analysing thermogenic mechanism in brown adipose tissue. Actually, in addition to white adipose tissue which is the major type of adipose tissue, mammals own another type of adipose tissue referred to as brown adipose tissue. This later tissue is an activatable thermogenic organ which oxidizes fatty acids and releases heat in blood stream. Brown fat is activated during exposure to the cold (in rodents), at birth, and during arousal in hibernators. My initial work helped to characterize a mitochondrial protein named uncoupling protein or UCP which is responsible for activation of fatty acid oxidation and heat production in brown adipocytes. Actually, in most cells, fifty per cent of oxidation energy is recovered as ATP in mitochondria through the process of coupling of respiration to ADP phosphorylation. In contrast to mitochondria of most tissues, brown adipocyte mitochondria can escape the obligatorily coupling of respiration and waste almost ninety per cent of respiration energy as thermogenesis. UCP characterization and its molecular cloning as well as antibodies obtention were used to better understand cellular thermogenesis. Brown adipocytes were identified in babies and adult patients with pheochromocytoma. More recently, research on the brown fat UCP helped us to identify UCP2, a UCP homolog present in most human and animal tissues. A family of UCPs exist in animals and plants. These UCPs may function as mitochondrial uncouplers. However, the ancient function of the UCPs may be rather associated to adaptation to oxygen and control of free radicals than to thermogenesis. Further studies of UCPs will improve the knowledge of mitochondrial metabolism and substrate oxidation. In other respects, analysis of molecular mechanisms controlling respiration uncoupling may contribute to new strategies of treatment of metabolic disorders such as obesity.