Epigallocatechin Gallate During Dietary Restriction — Potential Mechanisms of Enhanced Liver Injury

Abstract

Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called “fat burning” effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands’ cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the “drug-host” interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.

The Anti-Obesity Effect of Traditional Chinese Medicine on Lipid Metabolism

“…caused less damage to the liver than the unprocessed Polygonum multiflorum Thunb. ( Tu et al, 2015 ), while EGCG caused dose-dependent hepatotoxicity in mice under dietary restriction, but not in mice fed a normal diet ( Shi et al, 2020 ). In addition, Tripterygium wilfordii Hook.…”

“…The expression of PPARα and ApoA-Ⅰ was significantly downregulated in the hyperlipidemia group with tanshinone IIA treatment ( Yi-Xin et al, 2017 ). A high dose of Crataegus pinnatifida Bunge increased the expressions of ApoA-I gene and HDL-c in HFD-fed mice ( Shih et al, 2013 ). In addition, curcumin increased cholesterol efflux by activating and upregulating the expression of LXR and ABCA1 in subcutaneous adipocytes isolated from rabbits ( Dong et al, 2011 ).…”

Metabolomics Reveals Process of Allergic Rhinitis Patients with Single- and Double-Species Mite Subcutaneous Immunotherapy

“…Supplementation with C. butyricum increased the concentrations of essential amino acids and flavor amino acids, as well as AA, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and total PUFAs in breast muscle [51]. Epigallocatechin gallate (EGCG) could induce enhanced lipid metabolism pathways, and the combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites [52]. One of the major components in high-fat diets is the omega-6 PUFAs, called linoleic acid, which are metabolized to an array of eicosanoids and prostaglandins depending upon the enzymes in the pathway.…”

Multispectroscopic, virtual and in vivo insights into the photoaging defense mediated by the natural food colorant bixin

“…Moreover, no toxic side effects of bixin have been reported even at high concentrations 44 while EGCG has been reported to cause hepatotoxicity at higher dosage and other detrimental effects in several trials. 45,46 Earlier, we reported a dose-dependent effect of bixin on tyrosinase inhibition resulting in the loss of tyrosinase's helical structure, polypeptide unfolding and exposure of the hydrophobic region. 40 Thus, to study the probable binding site of bixin for collagenase, elastase, and hyaluronidase.…”