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, 10 (11), e0141227
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Green Tea Extract Rich in Epigallocatechin-3-Gallate Prevents Fatty Liver by AMPK Activation via LKB1 in Mice Fed a High-Fat Diet

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Green Tea Extract Rich in Epigallocatechin-3-Gallate Prevents Fatty Liver by AMPK Activation via LKB1 in Mice Fed a High-Fat Diet

Aline B Santamarina et al. PLoS One.

Abstract

Supplementation with epigallocatechin-3-gallate has been determined to aid in the prevention of obesity. Decaffeinated green tea extract appears to restore a normal hepatic metabolic profile and attenuate high-fat diet (HFD)-induced effects, thereby preventing non-alcoholic fatty liver disease in mice. Mice were maintained on either a control diet (CD) or HFD for 16 weeks and supplemented with either water or green tea extract (50 mg/kg/day). The body mass increase, serum adiponectin level, and lipid profile were measured over the course of the treatment. Furthermore, the AMPK pathway protein expression in the liver was measured. From the fourth week, the weight gain in the CD + green tea extract (CE) group was lower than that in the CD + water (CW) group. From the eighth week, the weight gain in the HFD + water (HFW) group was found to be higher than that in the CW group. Moreover, the weight gain in the HFD + green tea extract (HFE) group was found to be lower than that in the HFW group. Carcass lipid content was found to be higher in the HFW group than that in the CW and HFE groups. Serum analysis showed reduced non-esterified fatty acid level in the CE and HFE groups as compared with their corresponding placebo groups. Increased adiponectin level was observed in the same groups. Increased VLDL-TG secretion was observed in the HFW group as compared with the CW and HFE groups. Increased protein expression of AdipoR2, SIRT1, pLKB1, and pAMPK was observed in the HFE group, which explained the reduced expression of ACC, FAS, SREBP-1, and ChREBP in this group. These results indicate that the effects of decaffeinated green tea extract may be related to the activation of AMPK via LKB1 in the liver of HFD-fed mice.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Body composition: body mass gain; lean body mass; and subcutaneous fat accumulation.
(A) body mass gain over the 16 weeks of treatment with HFD; (B) lean body mass; (C) subcutaneous fat accumulation obtained from the carcass of different experimental groups. Data are expressed in mean ± s.e.m. *p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. $p<0.05 High-fat and Water (HFW) group versus CW group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group.
Fig 2
Fig 2. In vivo triacylglycerol production rate. After 16 week of treatment.
After 16 week of treatment, Triton WR1339 (400 mg/kg BW) was administered intravenously to 4 hours fasted mice. Samples collected at time 0, 30, 60, 90 and 120 min after injection. Plasma samples from each time point were used to determine plasma triacylglycerol levels over time (A). Triacylglycerol production (B) was estimated by calculated the AUC. Data are expressed in mean ± s.e.m.*p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. $p<0.05 High-fat and Water (HFW) group versus CW group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group.
Fig 3
Fig 3. Liver protein expression in different experimental groups of Laminin R, AdipoR2 and SIRT1.
Western Blotting analysis of protein expression in the liver on different experimental groups of membrane receptors (A) Laminin Receptor, (B) AdipoR2, and (C) SIRT1. Image shows demonstrative bands of the analyzed proteins and respective housekeeping protein (β-tubulin) in liver. Data are expressed in mean ± s.e.m. *p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group. $p<0.05 HFW versus CW.
Fig 4
Fig 4. Liver protein expression in different experimental groups of LKB1 / AMPK pathway.
Western blotting analysis of protein expression in the liver on different experimental groups of AMPK—LKB1 pathway (A) pLKB1, (B) LKB1, (C) pAMPKα, (D) AMPKα 1/2. Image shows demonstrative bands of the analyzed proteins and respective housekeeping protein (β-tubulin) in liver. Data are expressed in mean ± s.e.m. *p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group. $p<0.05 HFW versus CW.
Fig 5
Fig 5. Liver protein expression in different experimental groups of lipogenic enzymes.
Western Blotting analysis of protein expression in the liver on different experimental groups of enzymes responsible for synthesis of fatty acids and de novo lipogenesis. (A) pACC, (B) ACCα and (C) FAS. Image shows demonstrative bands of the analyzed proteins and respective housekeeping protein (β-tubulin) in liver. Data are expressed in mean ± s.e.m. *p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group. $p<0.05 HFW versus CW.
Fig 6
Fig 6. Liver protein expression of nuclear transcription factors of lipids metabolism in different experimental groups.
Western Blotting analysis of protein expression in the liver on different experimental groups of nuclear transcription factors involved in promotion of enzymes responsible for synthesis of fatty acids and de novo lipogenesis. (A) pSREBP-1c, (B) SREBP-1, (C) ChREBP. Image shows demonstrative bands of the analyzed proteins and respective housekeeping protein (β-tubulin) in liver. Data are expressed in mean ± s.e.m. *p<0.05 Control diet and EGCG (CE) group versus Control diet and Water (CW) group. #p<0.05 High-fat diet and EGCG (HFE) group versus HFW group. $p<0.05 HFW versus CW.
Fig 7
Fig 7. EGCG through adiponectin and LKB1 / AMPK pathway on lipid metabolism—possible mechanism.
Statement from mechanism by which EGCG promotes increase in adiponectin and performs activation on the signaling of AMPK via LKB1 inhibiting mediators responsible for the synthesis of fatty acids and de novo lipogenesis. (Liver and DNA- from FreeDigitalPhotos.net).

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Grant support

This work was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo 2014/19508-7 - grant to: Dr Lila Missae Oyama and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - grant to Aline Boveto Santamarina.
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