The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function

Brial, François; Alzaïd, Fawaz; Sonomura, Kazuhiro; Kamatani, Yoichiro; Meneyrol, Kelly; Lay, Aurélie Le; Péan, Noémie; Hedjazi, Lyamine; Sato, Taka Aki; Venteclef, Nicolas; Magnan, Christophe; Lathrop, Mark; Dumas, Marc; Matsuda, Fumihiko; Zalloua, Pierre; Guyader, Dominique

doi:10.1016/j.celrep.2020.01.066

Cited by 42 publications

(40 citation statements)

References 52 publications

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“…Although a receptor has not yet been identified, ImP was shown to directly inhibit hepatic insulin receptor substrate signalling in mice, with p38 mitogen-activated protein kinase (MAPK)-mediated hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) being identified as a central regulatory mechanism [ 98 ]. In a recent study in humans on the extreme end of cardiometabolic disease (obese and hyperglycaemic), the microbial metabolite 4-cresol negatively correlated with type 2 diabetes [ 99 ]. Although 4-cresol can be derived directly from food, it is also a product of tyrosine and phenylalanine fermentation in the colon.…”

Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

“…Although 4-cresol can be derived directly from food, it is also a product of tyrosine and phenylalanine fermentation in the colon. Subcutaneous administration of 4-cresol prevented development of hyperglycaemia and fatty liver in mice fed a high-fat diet [ 99 ]. In line with observations that 4-cresol increases insulin secretion, this metabolite downregulated the expression of dual-specificity tyrosine-regulated kinase-1a (DYRK1A) [ 99 ], which has been shown to facilitate pancreatic beta cell proliferation [ 100 ].…”

Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

“…Subcutaneous administration of 4-cresol prevented development of hyperglycaemia and fatty liver in mice fed a high-fat diet [ 99 ]. In line with observations that 4-cresol increases insulin secretion, this metabolite downregulated the expression of dual-specificity tyrosine-regulated kinase-1a (DYRK1A) [ 99 ], which has been shown to facilitate pancreatic beta cell proliferation [ 100 ]. In addition, Lactobacillus plantarum , Enterococcus faecalis and Bacteroides thetaiotaomicron produce LCFAs, including conjugated linoleic acids (CLAs) [ 101 ].…”

Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

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Intestinal microbial metabolites in human metabolism and type 2 diabetes

Herrema

Niess

2020

Diabetologia

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Humans with the metabolic syndrome and type 2 diabetes have an altered gut microbiome. Emerging evidence indicates that it is not only the microorganisms and their structural components, but also their metabolites that influences the host and contributes to the development of the metabolic syndrome and type 2 diabetes. Here, we discuss some of the mechanisms underlying how microbial metabolites are recognised by the host or are further processed endogenously in the context of type 2 diabetes. We discuss the possibility that gut-derived microbial metabolites fuel the development of the metabolic syndrome and type 2 diabetes.

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Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

Section: Gut Microbe-derived Metabolites Alter Endogenous Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Herrema

Niess

2020

Diabetologia

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“…In the past decade, both animal [ 3 , 4 ] and human [ 5 , 6 , 7 ] studies have recognized microbiota-derived metabolites—such as short chain fatty acids (SCFA), 4-cresol, and imidazole propionate—as potential drivers of insulin resistance in MetSyn and DM2 [ 2 , 8 , 9 , 10 , 11 ]. However, many questions remain.…”

Section: Introductionmentioning

confidence: 99%

Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition

et al. 2020

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Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial–metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn

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“…It was recently reported that metabolites produced by intestinal bacteria regulate β-cell functions in diabetes (39). In addition, foods fermented with koji mold activate intestinal bacteria (40).…”

Section: Discussionmentioning

confidence: 99%

Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

Yagi

Ataka

Cheng

et al. 2020

Food & Nutrition Research

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Background: Red rice koji (RRK), prepared by growing Monascus species on steamed rice, has been reported to lower blood glucose levels in diabetic animal models. However, the action mechanism is not yet completely understood. Objective: The objective of this study was to examine the mechanism underlying the hypoglycemic action of RRK extract in two diabetic animal models: the insulin-deficiency mice, where the insulin deficiency was induced by streptozotocin (STZ), and insulin-resistance mice, where the insulin resistance was induced by a high-fat diet (HFD). Design: Low (12.5 mg/kg body weight [BW]) and high (50.0 mg/kg BW) doses of RRK extract were orally administered to the mice for 10 successive days (0.25 mL/day/mouse). The protein expression levels of glucose transporter type 4 (GLUT4) in the skeletal muscle and glucose transporter type 2 (GLUT2) in the liver were measured. Blood glucose (BG) levels of STZ-treated mice in insulin tolerance test (ITT) and BG and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test (IPGTT) were investigated. Results: In the STZ-treated mice, oral administration of RRK extract lowered BG levels and food intake but increased plasma 1,5-anhydroglucitol level. Moreover, the RRK extract lowered the BG levels of STZ-treated mice as measured by ITT. In the HFD-fed mice, we confirmed that the orally administered RRK extract lowered the BG and the homeostasis model assessment index for insulin resistance. Furthermore, the RRK extract lowered the BG and insulin levels of HFD-fed mice in IPGTT. Regarding the protein levels of GLUT, the orally administered RRK extract increased the GLUT4 level in the skeletal muscle; however, the RRK extract did not alter the GLUT2 level in the liver of either the STZ-treated or the HFD-fed mice. Popular scientific summary • Red rice koji (RRK) extract lowered blood glucose levels in streptozotocin (STZ)-treated and highfat diet (HFD)-fed mice and food intake in STZ-treated mice. • RRK extract lowered blood glucose levels of STZ-treated mice in insulin tolerance test and blood glucose and insulin levels of HFD-fed mice in intraperitoneal glucose tolerance test. • RRK extract increased glucose transporter type 4 level in the skeletal muscle of both STZ-treated and HFD-fed mice.

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The Natural Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function

Cited by 42 publications

References 52 publications

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition

Red rice koji extract alleviates hyperglycemia by increasing glucose uptake and glucose transporter type 4 levels in skeletal muscle in two diabetic mouse models

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