Macronutrient-induced cascade of events leading to parallel changes in hypothalamic serotonin and insulin.

Extracellular serotonin (5-HT) and insulin from hypothalamic PVN-VMH region follow parallel changes in response to specific macronutrient ingestion. Possible independent or causal mechanisms have been investigated. A common primary event might be pancreatic insulin secretion for both insulin entry into the brain and 5-HT synthesis through variations in the ratio of tryptophan over competitor amino acids. The steps of this cascade were found to account only partly for the changes in hypothalamic 5-HT and insulin. The central consequences of these metabolic effects may be modulated directly at the hypothalamic level. For instance, we observed a positive relation between the changes in insulin and 5-HT and the satiating potency of each nutrient. In addition, a direct action of dexfenfluramine on insulin has been found at the hypothalamic level showing that an activation of the serotonergic system immediately enhances insulin levels. This central event may be an important step in a cascade of events triggered by macronutrient ingestion leading to common hypothalamic insulin and 5-HT changes involved in feeding regulation.