10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

Goto, Tsuyoshi; Kim, Young Il; Furuzono, Tomoya; Takahashi, Nobuyuki; Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia; Ohue, Ryuji; Nomura, Wataru; Sugawara, Tatsuya; Yu, Rina; Kitamura, Nahoko; Park, Si‐Bum; Kishino, Shigenobu; Ogawa, Jun; Kawada, Teruo

doi:10.1016/j.bbrc.2015.02.154

Cited by 67 publications

(48 citation statements)

References 34 publications

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“…The present study establishes TRPV1 as an essential target for KetoA-mediated browning in WAT; however, several molecules have been identified to work as fatty acid receptors, including nuclear receptors and GPRs, many of which have been shown to play a critical role in the regulation of whole-body glucose and lipid metabolisms (51). Recently, we reported that KetoA could activate PPARa and PPARg (17) in culture cells. Activation of both PPARa and PPARg is useful for the management of obesity-related metabolic disorders (36,52).…”

Section: Discussionmentioning

confidence: 50%

“…In addition, these fatty acids have been reported to possess specific biologic activities. For instance, oxo fatty acids activate a ligand-activated transcription factor, known as peroxisome proliferator-activated receptor (PPAR)g, in adipocytes (17). Similarly, HYA [10-hydroxy-12(Z)-octadecenoic acid] exerts anti-inflammatory effects via down-regulation of LPS-induced maturation in dendritic cells and the blocking of TNF-a-induced intestinal barrier impairment (18).…”

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confidence: 99%

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

et al. 2017

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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.

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Section: Discussionmentioning

confidence: 50%

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confidence: 99%

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

et al. 2017

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“…Serum linoleic acid was correlated with HMW adiponectin in our study. It is suggested that linoleic acid and linoleic acid-derived fatty acids might increase serum adiponectin level through Keto A, which is a linoleic acid-derived fatty acid produced by gut lactic acid bacteria, and induce adipocyte differentiation via the activation of peroxisome proliferator-activated receptor γ (PPAR-γ) [27, 28]. This mechanism might be associated with the finding that pioglitazone, a PPAR-γ agonist, induced an increase in serum adiponectin level in humans [29].…”

Section: Discussionmentioning

confidence: 99%

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese

Fujii

Kawai

Azuma

et al. 2017

Journal of Diabetes Research

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Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r = −0.411, p < 0.0001), fasting glucose (r = −0.330, p < 0.0001), HbA1c (r = −0.231, p = 0.0146), and systolic blood pressure (r = −0.224, p = 0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r = −0.416, p < 0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

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“…Octadecenoic acid is the metabolite of linoic acid after gut micobiota metabolism. This metabolite (Goto et al, 2015) can stimulate adipogenesis and affect lipid rafts in the cell membranes that facilitates insulin signaling (Simons and Toomre, 2000). A high abundance of hexadecanoic acid (palmitic acid) has been shown to induce anxiety-like behaviors in mice (Moon et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomic patterns in patients with exhaustion disorder

Hadrévi

Jonsdottir

Jansson

et al. 2018

Stress

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Exhaustion disorder (ED) is a stress-related disorder that often implies a great burden on the individual patient as well as on society. Previous studies have shown that ED is associated with metabolic deviations, such as lowered fasting glucose. Several mechanisms have been discussed as a plausible explanation of the lack of energy described by these patients. Metabolic processes and reduced ability to mobilize energy have been suggested as important factors. This study investigated metabolomics in 20 patients diagnosed with ED and compared them with 21 healthy controls. Plasma metabolic profiles were examined in both fasting and nonfasting (postprandial) conditions. Blood plasma samples were analyzed for metabolite content using gas chromatography mass spectrometry. A total of 62 different metabolites were simultaneously detected in each of the samples. Multivariate models indicated systematic differences between patients with ED and healthy controls in both their fasting and nonfasting plasma metabolite levels. Lysine and octadecenoic acid were more abundant and glutamine, glycine, serine and gluconic acid were less abundant in the patients across both conditions. In the present study, we comprehensively and simultaneously screen for changes in a large number of metabolites. Our results show a difference in systemic metabolites between patients with exhaustion disorder and healthy controls both in the fasting and in the postprandial states. Here, we present new potential biomarkers mirroring exhaustion disorder metabolism. LAY SUMMARYExhaustion disorder (ED) patients suffer from stress-related symptoms including a reduced energy level. This study investigates the body's metabolism in patients with ED, both fasting and after a meal. New potential markers that may help future investigations on ED were identified. ARTICLE HISTORY

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10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

Cited by 67 publications

References 34 publications

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

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

Relationships between Composition of Major Fatty Acids and Fat Distribution and Insulin Resistance in Japanese

Plasma metabolomic patterns in patients with exhaustion disorder

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