Uncoupling protein (UCP) 3 is a mitochondrial inner membrane protein expressed predominantly in glycolytic skeletal muscles.Transgenic mice were created with a 16 kb region encompassing the human UCP3 gene. Changes in body weight, adiposity and glucose or insulin tolerance were assessed in mice fed chow and high-fat diets. Mitochondrial uncoupling was investigated on permeabilised muscle fibres. Indirect calorimetry was used to determine whole-body energy expenditure and substrate utilisation.