During the period 1955-1961, researchers established the central paradigm that hepatic and adipose metabolism are governed by a coordinated hormonal and nutrient signaling system. Studies showed ACTH stimulates lipolysis, glucocorticoids regulate hepatic glucose output, and feeding patterns modulate lipogenesis, highlighting an integrated endocrine-nutrient control of energy balance. This foundational period introduced chronometabolic concepts by linking timing, feeding status, and hormonal milieu to metabolic fluxes, using both isolated tissues and in vivo approaches.