Figure 1.

The complex molecular mechanism of action by which capsaicin may prevent the development of metabolic syndrome. In humans, TRPV1 activation may up-regulate Signal Transducer and Activator of Transcription-3 (STAT-3), a key member of the JAK/STAT pathway. Stimulation by cytokines of STAT-3 expressed in hepatocytes prevents steatosis. In animal studies, TRPV1 activation was linked to reduced fat accumulation and improved serum triglyceride (TG) and total cholesterol (TC) levels. Dietary capsaicin stimulates glucagon-like peptide-1 (GLP-1) secretion in the gastrointestinal tract. Furthermore, capsaicin supports the growth of the “anti-obesity bacterium”, Akkermansia muciniphila, by increasing mucin production, acting on the mucin-2 (Muc2) gene Activation of TRPV1 in preadipocytes results in lipid accumulation and increased insulin sensitivity via up-regulation of the Peroxisome Proliferator-Activated Receptor-γ (PPARγ), PPARγ-coactivator-1α (PGC-1α), and Uncoupling Protein-1 (UCP1) genes. Reproduced with permission from [95].