Effects of epigallocatechin-3-gallate on thermogenesis and mitochondrial biogenesis in brown adipose tissues of diet-induced obese mice

Abstract

Background: Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea and has been considered a natural agent that can help to reduce the risk of obesity. Objective: The aim of this study was to investigate the effects of EGCG on thermogenesis and mitochondrial biogenesis in brown adipose tissue (BAT) of diet-induced obese mice. Methods: Male C57BL/6J mice were provided a high-fat diet for 8 weeks to induce obesity, following which they were divided into two groups: one on a high-fat control diet and the other on a 0.2% EGCG (w/w)-supplemented high-fat diet for another 8 weeks. Results: The EGCG-supplemented group showed decreased body weight gain, and plasma and liver lipids. EGCG-fed mice exhibited higher body temperature and mitochondrial DNA (mtDNA) content in BAT. The messenger RNA levels of genes related to thermogenesis and mitochondrial biogenesis in BAT were increased by EGCG. Moreover, adenosine monophosphate-activated protein kinase (AMPK) activity in BAT was stimulated by EGCG. Conclusions: The results suggest that EGCG may have anti-obesity properties through BAT thermogenesis and mitochondria biogenesis, which are partially associated with the regulation of genes related to thermogenesis and mitochondria biogenesis, and the increase in mtDNA replication and AMPK activation in BAT of diet-induced obese mice.

Keywords: EGC; Gthermogenesis; brown adipose tissues; mitochondrial biogenesis; obesity.

Figure 1.

Body temperature of mice fed control or epigallocatechin-3-gallate (EGCG) diets for 8 weeks. After 8 weeks of dietary supplementation, body temperature was measured during exposure to 4°C for 6 h. Values are expressed as mean ± SEM (n = 6). *p < 0.05 vs control group. Control, high-fat diet; EGCG, 0.2% EGCG-supplemented high-fat diet.

Figure 2.

Mitochondrial DNA (mtDNA) content in brown adipose tissue of mice fed control or epigallocatechin-3-gallate (EGCG) diets for 8 weeks. Values for the EGCG group are expressed as the fold change compared with those for the control group (mean ± SEM, n = 6). *p < 0.05 vs control group. Control, high-fat diet; EGCG, 0.2% EGCG-supplemented high-fat diet.

Figure 3.

Relative messenger RNA (mRNA) levels of genes involved in (a) thermogenesis and (b) mitochondrial biogenesis in brown adipose tissue of mice fed control or epigallocatechin-3-gallate (EGCG) diets for 8 weeks. Values for the EGCG group are expressed as the fold change compared with those for the control group (mean ± SEM, n = 6). *p < 0.05, **p < 0.01 vs control group. Control, high-fat diet; EGCG, 0.2% EGCG-supplemented high-fat diet. UCP1, uncoupling protein 1; UCP2, uncoupling protein 2; PRDM16, PR domain containing 16; CPT-1β, carnitine-palmitoyl-coenzyme A transferase-1β; ACC2, acetyl-coenzyme A carboxylase-2; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1α; NRF1, nuclear respiratory factor-1; Tfam, mitochondrial transcription factor A.

Figure 4.

AMP-activated protein kinase (AMPK) activity in brown adipose tissue of mice fed control or epigallocatechin-3-gallate (EGCG) diets for 8 weeks. Values for the EGCG group are expressed as the fold change compared with those for the control group (mean ± SEM, n = 6). ***p < 0.001 vs control group. Control, high-fat diet; EGCG, 0.2% EGCG-supplemented high-fat diet.

Figure 5.

Schematic diagram showing the possible mechanisms(s) of brown adipose tissue thermogenesis and mitochondrial biogenesis by dietary epigallocatechin-3-gallate (EGCG) in diet-induced obese mice. AMPK, AMP-activated protein kinase; ACC2, acetyl-coenzyme A carboxylase-2; carnitine-palmitoyl-coenzyme A transferase-1; UCP1, uncoupling protein 1; UCP2, uncoupling protein 2; PRDM16, PR domain containing 16; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1α; NRF1, nuclear respiratory factor-1; Tfam, mitochondrial transcription factor A; mtDNA, mitochondrial DNA.