Systemic energy homeostasis is determined by the intricate interplay between different organ compartments, including the central nervous system, skeletal muscle, liver as well as white and brown adipose tissue. Indeed, the coordinated adaptation of metabolic pathways in different tissues to changing environmental cues is critical for systemic metabolic health. However, integrative molecular checkpoints in inter-tissue communication and/or coordination still remain largely unknown.
Here, we discuss our recent findings on both the hepatic and systemic roles of novel endocrine and transcriptional axes in energy homeostasis and metabolic dysfunction. Our data overall underline the notion that the coordinated regulation of distinct transcriptional hubs in liver may represent a key component of integrative inter-tissue communication in metabolic complications associated with obesity and cancer cachexia.