Theaflavin-3,3′-digallate, a black tea polyphenol, stimulates lipolysis associated with the induction of mitochondrial uncoupling proteins and AMPK–FoxO3A–MnSOD pathway in 3T3-L1 adipocytes

Abstract

Phytochemicals have gained an immense interest in obesity management. Previously, we have shown that theaflavin-3,3′-digallate (TF3), a black tea polyphenol, prevents adipocyte-triggered metaflammation. Here, we demonstrate that TF3 attenuates triacylglycerol accumulation in adipocytes, concomitant with promoting gene expression profile that favors lipolysis and β-oxidation, and inducing energy dissipation-related genes, mitochondrial uncoupling protein-1 (UCP-1) and UCP-2. The gene expression is in line with the upregulation of peroxisome proliferator-activated receptor α (PPARα), a primary transactivator for the expression of lipolytic genes. TF3 activates AMP-activated protein kinase (AMPK), which is required for TF3 effects of PPARα upregulation, and the reversal of the inactivation of Forkhead-box-O 3A (FoxO3A) and insulin-induced suppression of manganese superoxide dismutase (MnSOD). The role of MnSOD in adipogenesis is verified in MnSOD-overexpressing adipocytes. Thus, our results demonstrate TF3 as a potent AMPK activator with anti-adiposity activity in adipocytes, suggesting its potential application in functional foods and nutraceuticals for obesity management.