Exercise and training lead to increases in daily energy requirements and fuel oxidation. Exercise and training also lead to a molecular adaptation in the muscle which influences important muscle qualities such as strength and endurance. In this module it will first be explained which methods are in use to quantify fuel oxidation, which insights these quantification methods have brought in the use of fuels during and following various forms of acute exercise, and what the consequences are of regular exercise and disuse for health. In the second part of the module focus will be on the metabolic and molecular adaptation that occurs in the muscle in response to endurance exercise and resistance exercise, and in response to disuse (too little exercise) and excess calorie intake. Special attention will be given to the mechanisms that lead to obesity, insulin resistance and type 2 diabetes and the signals and signalling routes that lead to these adaptations and metabolic diseases.