10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1

Gut microbiota can regulate the host energy metabolism; however, the underlying mechanisms that could involve gut microbiota–derived compounds remain to be understood. Therefore, in this study, we investigated the effects of KetoA [10-oxo-12(Z)-octadecenoic acid]—a linoleic acid metabolite produced by gut lactic acid bacteria—on whole-body energy metabolism and found that dietary intake of KetoA could enhance energy expenditure in mice, thereby protecting mice from diet-induced obesity. By using Ca2+ imaging and whole-cell patch-clamp methods, KetoA was noted to potently activate transient receptor potential vanilloid 1 (TRPV1) and enhance noradrenalin turnover in adipose tissues. In addition, KetoA up-regulated genes that are related to brown adipocyte functions, including uncoupling protein 1 (UCP1) in white adipose tissue (WAT), which was later diminished in the presence of a β-adrenoreceptor blocker. By using obese and diabetic model KK-Ay mice, we further show that KetoA intake ameliorated obesity-as...