Thermogenesis and appetite regulation pathways

Thermogenesis and appetite regulation pathways refer to a complex physiological network rather than a single molecular target, involving multiple receptors and tissues to maintain energy homeostasis (Morton et al., Nature, 2006). The central hub for this regulation is the hypothalamus, where anorexigenic POMC neurons and orexigenic AgRP neurons integrate peripheral signals from hormones like leptin and GLP-1 (Gautron & Elmquist, Crit Care Med, 2011). These pathways coordinate food intake with energy expenditure by modulating the sympathetic nervous system's effect on brown adipose tissue, primarily through the activation of Uncoupling Protein 1 (UCP1) (Cannon & Nedergaard, Physiol Rev, 2004). While not a single target, specific components within these pathways, such as the Melanocortin 4 receptor (MC4R) and Glucagon-like peptide-1 receptor (GLP-1R), are major therapeutic targets for obesity and type 2 diabetes (Müller et al., Mol Metab, 2022). Drugs like semaglutide and setmelanotide act on these specific receptors to achieve weight loss, though they must be monitored for cardiovascular and gastrointestinal side effects (Drucker, Cell Metab, 2016; Greenfield et al., J Clin Invest, 2009).

Other names

Energy balance pathwaysHypothalamic-adipose axisAppetite-thermogenesis regulatory networkMetabolic homeostasis pathways

Modulation of hypothalamic satiety centers (e.g., via GLP-1R and MC4R agonists) to reduce caloric intake and sympathetic activation of thermogenic adipose tissue (e.g., via ADRB3 agonists) to increase energy expenditure.