Phytosterols in human health: Biochemical mechanisms of action and disease-modulating effects

Figure 1 Molecular mechanisms underlying the metabolic and anti-inflammatory effects of phytosterols. Phytosterols regulate multiple cellular signaling pathways involved in metabolic homeostasis and inflammation. These mechanisms include activation of liver X receptors, which enhances cholesterol efflux through ATP-binding cassette transporter A1 and ABCG1 and promotes reverse cholesterol transport; modulation of peroxisome proliferator-activated receptors (α/γ), which improves fatty acid oxidation and insulin sensitivity; and activation of AMP-activated protein kinase, resulting in suppression of lipogenesis and stimulation of energy metabolism. In addition, phytosterols alter membrane lipid raft organization, influencing receptor-mediated signaling and inflammatory pathways. Emerging evidence also indicates that phytosterols modulate gut microbiota composition and bile acid signaling through pathways involving the farnesoid X receptor and Takeda G protein-coupled receptor 5, contributing to improved metabolic regulation. Collectively, these mechanisms lead to reduced low-density lipoprotein cholesterol levels, decreased hepatic lipid accumulation, improved insulin sensitivity and glucose uptake, and attenuation of systemic inflammation, ultimately supporting cardiometabolic health. ABCA1: ATP-binding cassette transporter A1; ACC: Acetyl-CoA carboxylase; AMPK: AMP-activated protein kinase; FXR: Farnesoid X receptor; LDL-C: Low-density lipoprotein cholesterol; LXR: Liver X receptors; PPAR: Peroxisome proliferator-activated receptors; SREBP-1c: Sterol regulatory element-binding protein-1c; TGR5: Takeda G protein-coupled receptor 5.