Many diseases are related to unequal input/output balance, imbalance/lack of macronutrients, toxic compounds or physical inactivity. The different organs involved in keeping homeostasis (brain-gut/microbiome-fat-liver-muscle) are tightly communicating with each other via peptides, proteins, nutrients and nerves (adipokines, hepatokines, myokines, gut peptides, neurotransmitters). Understanding the communication of this organ cross talk might decipher the molecular mechanisms in the pathogenesis of metabolic diseases like diabetes and obesity/metabolic syndrome. Furthermore, the increased energy storages lead to inflammation affecting the signaling cascades. Our mission is to elucidate the communication signals and pathways which might lead to novel therapeutic targets and new strategies for the prevention of these diseases.