title: Dietary (-)-Epigallocatechin-3-gallate Supplementation Counteracts Aging-Associated Skeletal Muscle Insulin Resistance and Fatty Liver in Senescence-Accelerated Mouse.
abstract: 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.
authors.affiliation: Department of Life Sciences, National Cheng Kung University , Tainan, Taiwan.
authors.forename: Hung-Wen
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Food and Nutrition, Providence University , Taichung, Taiwan.
authors.forename: Yin-Ching
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Department of Food and Nutrition, Providence University , Taichung, Taiwan.
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, National Cheng Kung University , Tainan, Taiwan.
authors.forename: Chu-Chun
authors.initials: CC
authors.lastname: Wei
authors.affiliation: Department of Life Sciences, National Cheng Kung University , Tainan, Taiwan.
authors.forename: Sue-Joan
authors.initials: SJ
authors.lastname: Chang
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019587:Dietary Supplements / Q000032:analysis*; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D010936:Plant Extracts; C495693:Slc2a4 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D002392:Catechin; C045651:epigallocatechin gallate; D005947:Glucose
keywords: EGCG; aging; insulin resistance; senescence accelerated mouse