Metabolic and humoral mechanisms of feeding and genesis of the ATP/ADP/AMP concept

The organization of the regulatory system of feeding and of the parallel metabolic changes is schematized by a cyclical cartoon depicting the 8 phases of regulation. As I proposed in1974, the cycle starts with the detection by hypothalamic sensors of decrease of the ATP/ADP/AMP turnover that reflects the post-prandial slow decline of general metabolic rate. That detection is translated into a signal of hunger. Experimental evidence is provided. Once initiated, this ‘basic’ signal follows the 7 remaining steps of the cycle, particularly the steps 2 and 4, where it receives multiple ‘modulating’ positive and negative signals (particularly peptides) that inform the central regulator, on the state of peripheral organs such as the adipocytes, stomach, intestine, and liver, on the outside world like day/light and on the available foods. Particular attention is given to the homeostatic and “homeoreutic” (see definition in the text) regulation of adipose reserves that are announced to brain specialized glio-neuronal “lipo-counters”. The role of insulin alongside leptin is shown. The conception of a part of the above mechanisms postulates and shows that some specialized glio-neuronal populations in the antero-ventral hypothalamus share metabolic properties along with somatic cells. Finally, the signal resulting from the algebraic sum of the main (the metabolic) signal and of the modulating pluses and minuses (peptides) leaves the integrative units and reaches the efferent phases (steps 5 and 6) that finish by inducing both metabolic adjustments and consequently food intake. The last steps (4 to 8) are only shortly commented.

Research highlights► In 1974 the idea that the ATP/ADP/AMP turnover was the initial signal for feeding. ► Invention of a metabolic device that substantiated this ATP/ADP, ischymetric idea. ► Extension of this ATP/ADP idea as a mechanism of sleep/wake like in feeding. ► In 1976 discovered that insulin was an anorexigen if hypoglycemia were prevented. ► In 1978 insulin perfusion in VMH results in hyporexia and permanent underweight.