Hypoglycemic and lipid lowering effects of theaflavins in high-fat diet-induced obese mice

Cai, Xiaqiang; Liu, Zeng-Hui; Dong, Xu; Wang, Ying; Zhu, Luwei; Li, Mengli; Xu, Yan

doi:10.1039/d1fo01966j

Cited by 27 publications

(28 citation statements)

References 33 publications

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“…SIRT6 is an NAD + -dependent deacetylase regulating hepatic glucose and lipid metabolism [ 24 ]. Cai et al reported that theaflavins decreased the expression of SIRT6 to reduce lipid accumulation [ 49 ]. Khan et al confirmed that SIRTP6 regulates fatty acid transport by inhibiting PPARγ [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Large Yellow Tea Extract Ameliorates Metabolic Syndrome by Suppressing Lipogenesis through SIRT6/SREBP1 Pathway and Modulating Microbiota in Leptin Receptor Knockout Rats

Sun

Cheng

et al. 2022

Foods

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Metabolic syndrome is a chronic metabolic disorder that has turned into a severe health problem worldwide. A previous study reported that large yellow tea exhibited better anti-diabetic and lipid-lowering effects than green tea. Nevertheless, the potential mechanisms are not yet understood. In this study, we examined the prevention effects and mechanisms of large yellow tea water extract (LWE) on metabolic syndrome using leptin receptor knockout (Lepr−/−) rats. Seven-week-old male Lepr−/− and wild type (WT) littermate rats were divided into Lepr−/− control group (KO) (n = 5), Lepr−/− with LWE-treated group (KL) (n = 5), WT control group (WT) (n = 6), and WT with LWE intervention group (WL) (n = 6). Then, the rats were administered water or LWE (700 mg/kg BW) daily by oral gavage for 24 weeks, respectively. The results showed that the administration of LWE significantly reduced the serum concentrations of random blood glucose, total cholesterol, triglyceride, and free fatty acids, and increased glucose tolerance in Lepr−/− rats. Moreover, LWE remarkably reduced hepatic lipid accumulation and alleviated fatty liver formation in Lepr−/− rats. A mechanistic study showed that LWE obviously activated SIRT6 and decreased the expression of key lipogenesis-related molecules SREBP1, FAS, and DGAT1 in the livers of Lepr−/− rats. Furthermore, LWE significantly improved microbiota dysbiosis via an increase in gut microbiota diversity and an abundance of the microbiota that produce short chain fatty acids (SCFAs), such as Ruminococcaceae, Faecalibaculum, Intestinimonas, and Alistipes. Finally, LWE supplementation increased the concentrations of SCFAs in the feces of Lepr−/− rats. These results revealed that LWE attenuated metabolic syndrome of Lepr−/− rats via the reduction of hepatic lipid synthesis through the SIRT6/SREBP1 pathway and the modulation of gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Large Yellow Tea Extract Ameliorates Metabolic Syndrome by Suppressing Lipogenesis through SIRT6/SREBP1 Pathway and Modulating Microbiota in Leptin Receptor Knockout Rats

Sun

Cheng

et al. 2022

Foods

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“…At a recent time, the effect of TFs extracted and purified from black tea was studied in high-fat diet–induced obese mice, and the results demonstrated that gavage administration of TFs might exert antihyperglycemic and lipid-lowering effects by inhibiting the synthesis and accumulation of lipids in the liver with activation of related pathways. Compared to other monomers of theaflavins, TF3 was proved to be the best choice ( Cai et al, 2021 ). Our previous research in vitro also reported that TF3 is the best one among the theaflavin constituents in alleviating hepatocyte lipid deposition through activating an AMPK signaling pathway by inhibiting plasma kallikrein ( Zhang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

Zhou

Zhang²,

Lin³

et al. 2022

Front. Pharmacol.

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Nonalcoholic fatty liver disease (NAFLD), one of the risk factors for hepatitis, cirrhosis, and even hepatic carcinoma, has been a global public health problem. The polyphenol compound theaflavin-3,3′-digallate (TF3), mainly extracted from black tea, has been reported to produce an effect on hypoglycemic and antilipid deposition in vitro. In our study, we further investigated the function and novel mechanisms of TF3 in protecting NAFLD in vivo. By using leptin-deficient obese (ob/ob) mice with NAFLD symptoms, TF3 treatment prevented body weight and waistline gain, reduced lipid accumulation, and alleviated liver function injury, as well as decreased serum lipid levels and TG levels in livers in ob/ob mice, observing no side effects. Furthermore, the transcriptome sequencing of liver tissue showed that TF3 treatment corrected the expression profiles of livers in ob/ob mice compared with that of the model group. It is interesting to note that TF3 might regulate lipid metabolism via the Fads1/PPARδ/Fabp4 axis. In addition, 16S rRNA sequencing demonstrated that TF3 increased the abundance of Prevotellaceae_UCG-001, norank_f_Ruminococcaceae, and GCA-900066575 and significantly decreased that of Parvibacter. Taken together, the effect of TF3 on NAFLD might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota. TF3 might be a promising candidate for NAFLD therapy.

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“…A TF mixture (25 mg/kg/day) improved impaired glucose tolerance and significantly lower blood glucose levels in prediabetic SDT rats, and increased insulin expression via the inhibition of gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) degradation [ 52 ]. Treatment with TFs reduced blood glucose levels and improved insulin resistance in mice, significantly reduced serum total cholesterol (TC), total cholesterol (TG), and low-density lipoprotein (LDL) levels, and inhibited alanine amino transferase (ALT), aspartate amino transferase (AST) activity [ 51 ]. The expression levels of sterol regulatory element-binding transcription factor 1 (SREBP-1), fatty acid synthase (FASN), which increases the expression of sirtuin 6 (SIRT6), were increased [ 51 ] High-fat diets and streptozotocin-induced diabetic rats were treated with different doses of TFs (25, 50, and 100 mg/kg b.wt/day) for 30 days, which resulted in glycated hemoglobin, hemoglobin, and glycoproteins (hexose, hexosamine, polystyrene and sialic acid), TCA cycle enzymes (isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, succinate dehydrogenase and malate dehydrogenase) returned to near-normal levels, and the decreased homeostatic model assessment of insulin resistance (HOMA-IR) index in a dose-dependent manner [ 53 ].…”

Section: Metabolic Syndrome and Theaflavinsmentioning

confidence: 99%

Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome

Shi

et al. 2022

IJMS

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In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.

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Hypoglycemic and lipid lowering effects of theaflavins in high-fat diet-induced obese mice

Abstract: Theaflavins (TFs) are the characteristic components of black tea and have been widely acquainted for their health benefits. The current study aimed to investigate the effects and mechanism of...

Cited by 27 publications

References 33 publications

Large Yellow Tea Extract Ameliorates Metabolic Syndrome by Suppressing Lipogenesis through SIRT6/SREBP1 Pathway and Modulating Microbiota in Leptin Receptor Knockout Rats

Large Yellow Tea Extract Ameliorates Metabolic Syndrome by Suppressing Lipogenesis through SIRT6/SREBP1 Pathway and Modulating Microbiota in Leptin Receptor Knockout Rats

Effect of theaflavin-3,3′-digallate on leptin-deficient induced nonalcoholic fatty liver disease might be related to lipid metabolism regulated by the Fads1/PPARδ/Fabp4 axis and gut microbiota

Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome

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