PYY, Insulin, and Thermogenesis Signaling Pathways

The PYY, Insulin, and Thermogenesis Signaling Pathways represent a coordinated physiological network responsible for maintaining energy homeostasis. Peptide YY (PYY), specifically the PYY3-36 isoform, is secreted by intestinal L-cells in response to food intake and acts as a satiety signal by binding to the Neuropeptide Y receptor type 2 (Y2R) in the arcuate nucleus of the hypothalamus (PMID: 12110890). Insulin, while primarily known for its role in peripheral glucose disposal via the insulin receptor, also acts centrally to inhibit appetite and can influence thermogenic activity in brown adipose tissue (BAT) (PMID: 24119848). Thermogenesis is the process of heat production, largely mediated by Uncoupling Protein 1 (UCP1) in BAT, which uncouples oxidative phosphorylation from ATP production to dissipate energy as heat (PMID: 11316783). Dysregulation within these intersecting pathways is a hallmark of obesity and metabolic disorders, making them a primary focus for multi-receptor agonist therapies aimed at simultaneous appetite suppression and increased caloric expenditure.

Other names

Energy homeostasis signaling networkMetabolic regulatory pathwaysAppetite and thermogenic signaling

Modulation of energy balance through the activation of Neuropeptide Y receptor type 2 (Y2R) by PYY to induce satiety, the activation of the Insulin Receptor (INSR) to regulate glucose uptake and central energy signaling, and the stimulation of Uncoupling Protein 1 (UCP1) in brown adipose tissue to increase energy expenditure via thermogenesis.