Mechanisms behind GLP-1 induced weight loss

Endogenous glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in maintaining pancreatic function as well as caloric intake. Since the advent of GLP-1 receptor agonists resistant to dipeptidyl peptidase-4 (DPP-4) (degradation, it has become clear that their chronic use promotes negative energy balance. With regard to their effects on body weight, the principal action of GLP-1 agonists is mediated via their inhibition of eating. In searching for the underlying mechanism of GLP-1 receptor agonist-induced anorexic effect, scientists have discovered pathways in the central nervous system, as well as in the periphery. This review describes emerging knowledge of a peripheral endocrine GLP-1 system mediating its activity through a central ascending GLP-1 pathway and targeting hypothalamic sites involved in the regulation of energy homeostasis. Thus peripheral and central GLP-1 sensitive pathways appear to be organised to co-operatively help control food intake and body weight.