<scp>l</scp>-Theanine regulates glucose, lipid, and protein metabolism <i>via</i> insulin and AMP-activated protein kinase signaling pathways

Li, Gang; Zeng, Li; An, Liu; Peng, Yingqi; Yuan, Dongyin; Zhang, Sheng; Li, Yinhua; Chen, Jinhua; Xiao, Wenjun; Gong, Zhihua

doi:10.1039/c9fo02451d

Cited by 41 publications

(50 citation statements)

References 51 publications

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“…The longevity protein SIRT1 is required for AMPK activity [69]. We have previously shown that L-theanine has protective effects in the livers of D-galactose-treated rats and promotes glucose metabolism through the AMPK signaling pathway, resulting in reduced sugar concentrations in the body [26,27]. Therefore, we speculate that L-theanine can inhibit the positive reaction of Schiff base formation between D-galactose and free amino groups, along with its reduction of AGEs and Aβ 1-42 concentrations, thereby alleviating D-galactose-induced damage in rats' brain tissues.…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, in vitro studies have shown that L-theanine reduces AGE formation [25]. We have previously reported that Ltheanine can protect the liver, promote AGE metabolism, and reduce the amount of AGEs in the liver and serum by maintaining the balance between oxidative stress and inflammation in the liver tissues of D-galactose-induced model rats [26,27]. However, D-galactose can circulate in the blood, therefore reaching various tissues and organs and form AGEs [1,8].…”

Section: Introductionmentioning

confidence: 98%

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l-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways

Zeng

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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The maintenance of homeostasis is essential for mitigating stress and delaying degenerative diseases such as Alzheimer’s disease (AD). AD is generally defined as the abnormal production of β-amyloid (Aβ) and advanced glycation end products (AGEs). The effects of l-theanine on Aβ and AGE generation were investigated in this study. Decreased AGEs and Aβ1-42 levels were reflected by increased acetylcholine (ACh) concentration and acetylcholinesterase (AChE) activity inhibition compared to model rats. l-Theanine also inhibited nuclear factor-κB (p65) protein expression by activating sirtuin1 (SIRT1), reducing inflammatory factor expression, and downregulating the mRNA and protein expression of AGE receptors (RAGE). Superoxide dismutase 2 and catalase protein expressions were markedly upregulated by l-theanine, whereas oxidative stress-related injury was alleviated. The expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) was also found to be increased. H&E staining showed that the apoptosis of hippocampal neurons was mitigated by decreased Bax and cleaved-caspase-3 protein expression and the increase of Bcl-2 protein expression. Moreover, l-theanine increased the gene and protein expression of brain-derived neurotrophic factor (BDNF). These findings suggest that the potential preventive effects of l-theanine against AD may be attributed to its regulation of SIRT1 and BDNF proteins and its mitigation of AGEs/RAGE signaling pathways in the brain tissue of AD model rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

l-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways

Zeng

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Previous studies have reported that L-theanine can inhibit obesity in mice [13], regulate lipid metabolism in normal rats [15], reduce the risk of T2DM development in human [12]. Recent study indicated that Ltheanine can activate the browning of white adipose tissue [16] and modulation of gut microbiota [17] in obesity mice.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that L-theanine can suppress fat accumulation in mice [13], and affect the absorption of lipids by regulating the expression of intestinal fatty acid transporters in rats [14]. Ltheanine also can regulate glucose, lipid, and protein metabolism via insulin and AMP-activated protein kinase (AMPK) signaling pathway in normal rats [15]. Recent studies demonstrate that L-theanine can activate the browning of inguinal white adipose tissue through upregulating the expression of thermogenic genes, thus ameliorates diet-induced obesity in mice [16].…”

Section: Introductionmentioning

confidence: 99%

L-theanine Prevents Progression of Nonalcoholichepatic Steatosis by Regulating Hepatocyte Lipid Metabolic Pathways via the CaMKKβ-AMPK Signaling Pathway

Jiang

Liu

et al. 2021

Preprint

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Background: L-theanine, a non-protein amino acid found principally in the green tea, has been previously shown to possess potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism. Methods: In vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of TG, accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo.Results: Our data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced Non-alcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK via its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ). Conclusions: Taken together, our findings suggest that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.

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“…AMPK is a crucial cellular energy sensor that has recently been demonstrated to be important in regulating the metabolic activity of brown-like adipocytes (21). It was found that the phosphorylation of AMPK was activated by L-theanine in mice livers (22). We therefore investigated the role of L-theanine in the activation of AMPK in adipocytes.…”

Section: Ampk Activation Is Indispensable For L-theanine-induced Browning Of Adipocytesmentioning

confidence: 99%

l-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice

Peng

Xiao

et al. 2021

Diabetes

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l-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with l-theanine (100 mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1, and other thermogenic genes. Meanwhile, administration of the mice with l-theanine increased energy expenditure. In vitro studies indicated that l-theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of l-theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. l-theanine treatment enhanced AMPKα phosphorylation both in adipocytes and iWAT. Knockdown of AMPKα abolished l-theanine–induced upregulation of Prdm16 and adipocyte browning. l-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for l-theanine–induced increase of α-KG and DNA demethylation on the Prdm16 promoter. Moreover, intraperitoneal administration with l-theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol, and free fatty acids in the high-fat diet–fed mice. Our results suggest a potential role of l-theanine in combating diet-induced obesity in mice, which may involve l-theanine–induced browning of WAT.

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l-Theanine regulates glucose, lipid, and protein metabolism via insulin and AMP-activated protein kinase signaling pathways

Abstract: LTA can regulate the metabolism of glucose, lipids and proteins by activating insulin and AMPK signaling pathways.

Cited by 41 publications

References 51 publications

l-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways

l-Theanine Ameliorates d-Galactose-Induced Brain Damage in Rats via Inhibiting AGE Formation and Regulating Sirtuin1 and BDNF Signaling Pathways

L-theanine Prevents Progression of Nonalcoholichepatic Steatosis by Regulating Hepatocyte Lipid Metabolic Pathways via the CaMKKβ-AMPK Signaling Pathway

l-Theanine Activates the Browning of White Adipose Tissue Through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-Induced Obesity in Mice

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