Green tea extract induces thermogenic phenotype by modulating the initial phases of the adipogenic process

Introduction: The development of thermogenic/beige adipocytes in white adipose tissue (WAT) might reduce the adverse effects of obesity and could help to improve metabolic health. Certain pharmacological and nutritional agents can promote those effects by activating transcription factors or regulatory signaling pathways furthering WAT browning. Albeit the connection between body weight (BW) loss and green tea (GT) have been well established, their potential contributions to the development of thermogenic/beige cells have been scarcely investigated. Objective: The aim of this study was to evaluate the relationship between metabolic alterations induced by an obesogenic diet and the induction of thermogenic/beige cells in GT-treated obese mice. Methodology: Male C57Bl/6 mice (3 months) were divided into 3 groups: Control (chow diet), Obese (cafeteria diet) and Obese+GT. The obese mice were fed with cafeteria diet for 4 weeks. After this period, the animals received gavage with GT (500 mg/Kg of BW) over 12 weeks (5 days/week). After 16 weeks of experimentation, mice were killed and the tissues were properly stored. We also evaluated the effect of a mix containing the main catechins found in GT (EGCG (2µM), EGC (1µM), ECG (0.6µM) and EC (0.4µM)) (Sigma) in a final concentration of 4 µM and a GT extract at 0.19% in the induction of beige phenotype in vitro (3T3-F442A pre-adipocytes). Results: Obese-induced mice that were treated with GT showed a significant reduction in indicators of obesity such as BW gain, fat depots, hyperlipidemia and an increment in plasma adiponectin levels without alteration in food intake. The basal metabolic rate was increased as well as genes involved in fatty acid (FA) oxidation, thermogenesis and beige cells markers in the subcutaneous WAT of obese animals treated with GT. GT also decreased inflammation and endoplasmic reticulum stress induced by the diet and relief of insulin resistance. GT was able to induce a futile cycle through de novo lipogenesis to activate the thermogenic pathway in vivo and in vitro. The mix of catechins or the GT showed significant reduction of lipid accumulation and upregulated the expression of thermogenic markers related to FA oxidation and mitochondrial activation as well as oxygen consumption. The effects of GT and the mix of catechins occur in an autonomous manner and seems to be dependent on the initial mechanism in adipogenesis through PPARγ participation. Conclusions: Our study suggests that the metabolic alterations caused by GT ingestion induce energetic expenditure and compromise the final commitment of adipose cell, still in the initial stages of the adipogenesis process, with modulations involving the PPARγ pathway, associated to the activation of the futile cycle and induction of beige phenotype. These alterations culminate in an effective therapeutic strategy to combat obesity and its comorbidities.
Financial support: FAPESP 2012/20415-8; 2013/22293-0; 2016/12059-8.