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

Abstract

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()-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 Ca 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-associated metabolic disorders. In the absence of any observed KetoA-induced antiobesity effect or UCP1 up-regulation in TRPV1-deficient mice, we prove that the antiobesity effect of KetoA was caused by TRPV1 activation-mediated browning in WAT. KetoA produced in the gut could therefore be involved in the regulation of host energy metabolism.-Kim, M., Furuzono, T., Yamakuni, K., Li, Y., Kim, Y.-I., Takahashi, H., Ohue-Kitano, R., Jheng, H.-F., Takahashi, N., Kano, Y., Yu, R., Kishino, S., Ogawa, J., Uchida, K., Yamazaki, J., Tominaga, M., Kawada, T., Goto, T. 10-oxo-12()-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, enhances energy metabolism by activation of TRPV1.

Role of TRPV1 in colonic mucin production and gut microbiota profile

“…Analysis also showed decreased overall abundance of beneficial lactic acid bacteria, including L. intestinalis, L. reuteri and L. gasseri , reflecting a compromised gut health in RTX group. Lactobacillus spp are reported to promote mucus secretion via producing metabolites like oxo-fatty acids (Kim et al, 2017), and also acts as probiotic and imparts gut health benefits (Kechagia et al, 2013). In another interesting finding, the Firmicutes/Bacteroidetes ratio in RTX group was decreased, which is reported to have opposite pattern in disorders like obesity (Castaner et al, 2018).…”

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo‐Fatty Acids Produced by Gut Bacteria Are Responsible for CCK Secretion in STC‐1 Cells via GPR40

“…Recent studies have revealed the physiological functions of fatty acid metabolites produced by gut lactic acid bacteria . Some of these metabolites were found in the mouse colon, as gut microbiota is located primarily in the distal intestine.…”

“…Recently, fatty acid derivatives (hydroxy‐ or oxo‐fatty acids) produced by gut lactic acid bacteria ( Lactobacillus plantarum ) have attracted a lot of attention for their favorable biological functions in both cell and animal models. Specific fatty acid derivatives can exert anti‐inflammatory effects, cytoprotective effects, modify lipid/energy metabolism, and protect gut barrier function . However, no current research is focused on the effect of those fatty acids on enteroendocrine function.…”

The Role of the Gut Microbiome in Energy Balance With a Focus on the Gut-Adipose Tissue Axis

“…The findings illustrate the interplay between gut microbiota and host energy metabolism via the metabolites of dietary omega-6-FAs, thereby shedding light on the prevention and treatment of metabolic disorders by targeting gut microbial metabolites. Another metabolite of linoleic acid that is involved in the regulation of host energy metabolism is 10-oxo-12(Z)-octadecenoic acid (Goto et al, 2015;Kim et al, 2017). It is produced by lactic acid bacteria in the intestine.…”