Dietary (−)-Epigallocatechin-3-gallate Supplementation Counteracts Aging-Associated Skeletal Muscle Insulin Resistance and Fatty Liver in Senescence-Accelerated Mouse

Aging is accompanied by pathophysiological changes including insulin resistance and fatty liver. Dietary supplementation with (−)-epigallocatechin-3-gallate (EGCG) improves insulin sensitivity and attenuates fatty liver disease. We hypothesized that EGCG could effectively modulate aging-associated c...

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Bibliographic Details
Published in:Journal of agricultural and food chemistry 2015-09, Vol.63 (38), p.8407-8417
Main Authors: Liu, Hung-Wen, Chan, Yin-Ching, Wang, Ming-Fu, Wei, Chu-Chun, Chang, Sue-Joan
Format: Article
Language:English
Subjects:
Aging - drug effects
Aging - metabolism
Animals
Camellia sinensis - chemistry
Catechin - administration & dosage
Catechin - analogs & derivatives
Dietary Supplements - analysis
Fatty Liver - drug therapy
Fatty Liver - genetics
Fatty Liver - metabolism
Female
Glucose - metabolism
Glucose Transporter Type 4 - genetics
Glucose Transporter Type 4 - metabolism
Humans
Insulin Resistance
Lipid Metabolism - drug effects
Liver - drug effects
Liver - metabolism
Male
Mice
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Plant Extracts - administration & dosage
Sterol Regulatory Element Binding Protein 1 - genetics
Sterol Regulatory Element Binding Protein 1 - metabolism
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Summary:Aging is accompanied by pathophysiological changes including insulin resistance and fatty liver. Dietary supplementation with (−)-epigallocatechin-3-gallate (EGCG) improves insulin sensitivity and attenuates fatty liver disease. We hypothesized that EGCG could effectively modulate aging-associated changes in glucose and lipid metabolism in senescence-accelerated mice (SAM) prone 8 (SAMP8). Higher levels of glucose, insulin, and free fatty acid, inhibited Akt activity, and decreased glucose transporter 4 (GLUT4) expression were observed in SAMP8 mice compared to the normal aging group, SAM resistant 1 mice. EGCG supplementation for 12 weeks successfully decreased blood glucose and insulin levels via restoring Akt activity and GLUT4 expression and stimulating AMPKα activation in skeletal muscle. EGCG up-regulated genes involved in mitochondrial biogenesis and subsequently restored mitochondrial DNA copy number in skeletal muscle of SAMP8 mice. Decreased adipose triglyceride lipase and increased sterol regulatory element binding proteins-1c (SREBP-1c) and carbohydrate responsive element binding protein at mRNA levels were observed in SAMP8 mice in accordance with hepatocellular ballooning and excess lipid accumulation. The pevention of hepatic lipid accumulation by EGCG was mainly attributed to down-regulation of mTOR and SREBP-1c-mediated lipid biosynthesis via suppression of the positive regulator, Akt, and activation of the negative regulator, AMPKα, in the liver. EGCG beneficially modulates glucose and lipid homeostasis in skeletal muscle and liver, leading to alleviation of aging-associated metabolic disorders.
ISSN:0021-8561
1520-5118
DOI:10.1021/acs.jafc.5b02501