Bioactive peptides and metabolic health: a mechanistic review of the impact on insulin sensitivity, lipid profiles, and inflammation

Abstract

Bioactive peptides, derived from dietary proteins including dairy, legumes, and marine sources, demonstrate various regulatory effects on metabolic homeostasis via specific biochemical interactions. These peptides improve insulin sensitivity by activating the IRS-1/PI3K/Akt pathway and facilitating AMPK-mediated GLUT4 translocation, while also influencing incretin hormones through CaSR-dependent GLP-1 secretion, DPP-4 inhibition, and digestive enzymes (α-amylase and α-glucosidase) inhibition. Their influence encompasses lipid metabolism, characterized by the suppression of cholesterol synthesis through HMG-CoA reductase downregulation and the promotion of fatty acid oxidation via PPARα/AMPK signaling. In addition to glucoregulation, bioactive peptides demonstrate significant anti-inflammatory and antioxidant effects through the inhibition of NF-κB/MAPK pathways, the scavenging of reactive oxygen species (ROS), and the activation of Nrf2-driven cytoprotective genes. They regulate adipokine signaling, including leptin sensitization and adiponectin secretion, as well as cardiometabolic hormones, such as angiotensin-converting enzyme inhibition and cortisol reduction. These mechanisms result in enhanced glycemic control, diminished adipose tissue dysfunction, and lowered cardiovascular risk. Bioactive peptides have shown efficacy in preclinical models and are promising nutraceutical candidates for the management of metabolic disorders such as type 2 diabetes, obesity, and atherosclerosis. Translational challenges, including oral bioavailability and dose optimization, require additional investigation to fully realize their therapeutic potential. Bioactive peptides play a significant role in metabolic regulation, particularly in enhancing insulin sensitivity. These compounds are increasingly recognized as nutraceuticals due to their potential effects on inflammation and hormone modulation.