In collaboration with Italian and Austrian colleagues (from the Venetian Institute of Molecular Medicine and the Universities of Padua, Graz, and Trieste) the researchers identified certain processes that are switched on at night by the regulators of the internal clock: "They include, for example, fat storage, glucose metabolism and insulin sensitivity," explains Henriette Uhlenhaut. At the same time, opposing processes such as fatty acid oxidation and protein breakdown are throttled down, according the authors. These patterns are especially pronounced in the hours before awakening and are thought to prepare the muscles for the day ahead. In the final step, the scientists investigated possible ways to intervene in these processes. To this end, they examined mice lacking these master regulators. Without a circadian clock, the animals were leaner, with less fat and more muscle mass. "Taken together, our work has revealed an entire metabolic network at multiple levels," Uhlenhaut explains. "Another biologically exciting finding is that, contrary to expectations, the key regulator is not centrally located in the brain, but is in fact the internal clock of the muscle cells themselves." In the long term, the authors will investigate the mechanisms also in humans and try to find a way for therapeutic interventions. Their hope is that it might be possible to counteract insulin resistance in type 2 diabetes or to stimulate energy use to combat obesity. - www.sciencedaily.com