Effect of epigallocatechin gallate on the body composition and lipid profile of down syndrome individuals: Implications for clinical management

Xicota, Laura; Rodríguez, Joaquín; Langohr, Klaus; Fitó, Montserrat; Dierssen, Mara; Torre, Rafael de la

doi:10.1016/j.clnu.2019.05.028

Cited by 26 publications

(28 citation statements)

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“…These results were consistent with previous studies showing that EGCG did not decrease body weight and BMI after 12 weeks of treatment in obese postmenopausal women 27 or could not prevent body weight and fat gains after treatment less than 12 months (3 and 6 months) in Down syndrome obese subjects. 61 However, a previous study showed that after 12 months of treatment in Down syndrome obese subjects, EGCG was effective in preventing body weight and body fat gains which were observed in the placebo group. 61 These results indicate that EGCG supplement for 8 weeks could not be effective in obesity reduction; however, a longer period of supplement might have a beneficial effect.…”

Section: Discussionmentioning

confidence: 94%

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects

Chatree

Sitticharoon

Maikaew

et al. 2020

Exp Biol Med (Maywood)

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Obesity is one of major risk factors increasing chronic diseases including type II diabetes, cardiovascular diseases, and hypertension. The effects of epigallocatechin gallate (EGCG), the major active compound in green tea, on reduced obesity and improved metabolic profiles are still controversial. Furthermore, the effects of EGCG on human adipocyte lipolysis and browning of white adipocytes have not been elucidated. This study aimed to investigate the effects of EGCG on obesity, lipolysis, and browning of human white adipocytes. The results showed that, when compared to the baseline values, EGCG significantly decreased fasting plasma triglyceride levels ( P < 0.05), systolic blood pressure ( P < 0.05), diastolic blood pressure ( P < 0.05), and serum kisspeptin levels ( P < 0.05) after 8 weeks of supplement. On the other hand, supplement of EGCG in obese human subjects for 4 or 8 weeks did not decrease body weight, body mass index, waist and hip circumferences, nor total body fat mass or percentage when compared to their baseline values. The study in human adipocytes showed that EGCG did not increase the glycerol release when compared to vehicle, suggesting that it had no lipolytic effect. Furthermore, treatment of EGCG did not enhance uncoupling protein 1 ( UCP1) mRNA expression in human white adipocytes when compared with treatment of pioglitazone, the peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, suggesting that EGCG did not augment the browning effect of PPAR-γ on white adipocytes. This study revealed that EGCG reduced 2 metabolic risk factors which are triglyceride and blood pressure in the human experiment. We also showed a novel evidence that EGCG decreased kisspeptin levels. However, EGCG had no effects on obesity reduction in humans, lipolysis, nor browning of human white adipocytes. Impact statement Obesity has become the worldwide problem that causes adverse health consequences in individuals. The effects of EGCG on decreased obesity and improved metabolic profiles are still inconclusive. This study revealed that EGCG decreased 2 metabolic risk factors including blood pressure and triglyceride in human obese subjects but had no effect on obesity reduction. This study also showed a novel finding that EGCG decreased kisspeptin levels in human obese subjects. The study in human adipocytes showed that EGCG had no effects on lipolysis nor browning of human white adipocytes. These findings might suggest that EGCG treatment ameliorated metabolic parameters but did not reduce obesity in obese humans. However, further studies are required to explore the relationship between the effect of EGCG on reduction of blood pressure and kisspeptin levels.

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Section: Discussionmentioning

confidence: 94%

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects

Chatree

Sitticharoon

Maikaew

et al. 2020

Exp Biol Med (Maywood)

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“…www.nature.com/scientificreports www.nature.com/scientificreports/ euploid mice, indicating that a high dosage of EGCG negatively affected the mechanical and material properties of all bones. A 12-month treatment of green tea extract containing ~9 mg/kg/day EGCG in humans with DS noted lowered bone mass, especially in females 21,42 . These and previous data noting adverse effects in bone properties after treatment with EGCG or green tea extracts containing EGCG 23,37 indicate that monitoring of bone parameters during and after treatment is warranted.…”

Section: Discussionmentioning

confidence: 99%

“…A meta-analysis of animal studies determined an acceptable daily intake of only 4.6 mg/kg/day EGCG using a strict safety standard 41 . An analysis of body composition in individuals with DS who were given green tea extract with ~9 mg/kg/day EGCG for 12 months showed a trend in males for less body weight gain and lower BMI at 12 months and 6 months after treatment was completed 21,42 . In general, it is evident that chronic treatment with EGCG or green tea extract is not without risk, and differences in EGCG serum concentrations between euploid and trisomic mice after a similar EGCG treatment in this study warrant quantification of EGCG levels www.nature.com/scientificreports www.nature.com/scientificreports/ Figure 6.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice

Goodlett

Stringer

LaCombe

et al. 2020

Sci Rep

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Epigallocatechin-3-gallate (EGCG) is a candidate therapeutic for Down syndrome (DS) phenotypes based on in vitro inhibition of DYRK1A, a triplicated gene product of Trisomy 21 (Ts21). Consumption of green tea extracts containing eGcG improved some cognitive and behavioral outcomes in DS mouse models and in humans with Ts21. In contrast, treatment with pure EGCG in DS mouse models did not improve neurobehavioral phenotypes. This study tested the hypothesis that 200 mg/kg/day of pure EGCG, given via oral gavage, would improve neurobehavioral and skeletal phenotypes in the Ts65Dn DS mouse model. Serum EGCG levels post-gavage were significantly higher in trisomic mice than in euploid mice. Daily EGCG gavage treatments over three weeks resulted in growth deficits in both euploid and trisomic mice. Compared to vehicle treatment, EGCG did not significantly improve behavioral performance of Ts65Dn mice in the multivariate concentric square field, balance beam, or Morris water maze tasks, but reduced swimming speed. Furthermore, EGCG resulted in reduced cortical bone structure and strength in Ts65Dn mice. These outcomes failed to support the therapeutic potential of EGCG, and the deleterious effects on growth and skeletal phenotypes underscore the need for caution in high-dose eGcG supplements as an intervention in DS.

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“…Nevertheless, it was found that pharmacological inhibition of brain DYRK1A can correct recognition memory deficits in three DS mouse models, all expressing an extra copy of Dyrk1a (Nguyen et al 2018 ; Kim et al 2016 ). Clinical trials in adults treated with epigallocatechin-3-gallate, a natural DYRK1a inhibitor from green tea, demonstrated a modest, but detectable gain of cognition in DS individuals (de la Torre et al 2014 , 2016 ; Xicota et al 2020 ).…”

Section: Potential Mechanisms Responsible For the Development Of Pseumentioning

confidence: 99%

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

Pecze

Randi

Szabó

2020

Mol Med

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Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms “Down syndrome” and “metabolite name” or “trisomy 21” and “metabolite name”. Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.

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Effect of epigallocatechin gallate on the body composition and lipid profile of down syndrome individuals: Implications for clinical management

Cited by 26 publications

References 28 publications

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects

Epigallocatechin gallate decreases plasma triglyceride, blood pressure, and serum kisspeptin in obese human subjects

Evaluation of the therapeutic potential of Epigallocatechin-3-gallate (EGCG) via oral gavage in young adult Down syndrome mice

Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome

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