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The liver–gut–brain axis is a physiological system specialized in fuel sensing and processing. Messenger molecules of diverse chemical composition and origin mediate cross-talks between these three organs. Our research aims to focus on this system and gain insight into the mechanisms by which nutrient-derived metabolites in general and bile acids, in particular, are sensed and integrated with the hormonal and neuronal system to coordinate overall energy utilization and homeostasis. At the subcellular level, our research indicates that mitochondria play a key role in mediating these responses. Understanding how these organelles are regulated is thus at the center of our research.