(−)-Epigallocatechin-3-O-gallate at a high concentration may induce lipolysis via ATP consumption by activation of stress defense mechanisms

Abstract

ABSTRACT Green tea catechins have thus far been demonstrated to have antiobesity effects in a variety of experimental models. However, upstream molecular events triggering those phenomena remain to be identified. In this study, we found that (−)-epigallocatechin-3-O-gallate (EGCG) promoted lipolysis in lipid-loaded Huh7 human hepatoma cells. Notably, EGCG at a high concentration induced both oxidative stress and protein stress (proteo-stress), leading to activation of stress defense mechanisms, such as mRNA expressions of antioxidant and phase-2 detoxifying enzymes, and heat shock proteins. Furthermore, EGCG decreased the level of intracellular ATP, while glucose uptake from culture media was promoted possibly for energy homeostasis. EGCG also upregulated the expression of adipose triglyceride lipase, and activated AMP-activated protein kinase. Collectively, these results suggest that EGCG induces lipolysis to compensate for ATP reduction derived from activation of stress defense systems against its oxidative and proteo-stress properties.