In this study, we investigated the activation of Transient receptor potential vanilloid subtype 1, TRPV1, by lactones, a representative flavor ingredient currently used for foods and beverages. As a result, we found that some lactones having C4 acyl chain length, gamma-octalactone, delta-nonalactone and beta-methyl-gamma-octalactone, gamma-undecalactone with C7 acyl chain length and delta-undecalactone with C6 acyl chain length activated TRPV1. TRPV1 is known as a non-selective cation channels that respond to a wide range of physical and chemical stimuli such as high temperature, protons, capsaicin and so on. Furthermore, it has been also demonstrated that activation of TRPV1 induced energy expenditure enhancement and thermogenesis, suppressed accumulation of visceral fat in mice and prevented non-alcoholic fatty acid liver. Thus, lactones that function as TRPV1 agonists are thought to be important candidates for decreasing the risks of developing a metabolic syndrome. (C) 2020 The Authors. Published by Elsevier Inc.