Dietary (‐)‐epigallocatechin‐3‐gallate (EGCG) supplementation counteracts metabolic disorders in senescence‐accelerated mouse

Abstract

Senescence‐accelerated mouse (SAM) prone 8 (SAMP8) displayed aging‐related insulin resistance has been reported; however, peripheral tissues like muscle and liver involved in modulation of glucose and lipid metabolism have not been reported in SAMP8 mice. Epigallocatechin gallate (EGCG) with anti‐diabetes was postulated to delay age‐related insulin resistance. Thus, dietary (3 months) EGCG supplementation (0.32% w:w) on the metabolic defects in skeletal muscle and liver were investigated in SAMP8 (n=15) mice compared to control diet SAMP8 mice (n=15) and SAM resistant 1 (SAMR1, n=8). Higher levels of fasting glucose, insulin and free fatty acid, inhibited Akt activity, and decreased GLUT4 protein expression were observed in SAMP8 mice compared to age‐matched SAMR1 mice. EGCG treatment successfully decreased blood glucose and insulin levels via restoring Akt activity and GLUT4 expression and increasing AMPK activity. Histological examination of the liver revealed hepatocellular ballooning and increasing lipid accumulation in SAMP8 mice. Hepatic triacylglycerol and ALT activities were higher in SAMP8 mice. Decreased ATGL (the gene for triglycerides hydrolysis) and increased SREBP1c and ChREBP1 (genes involved in de novo lipogenesis) in mRNA levels were observed in SAMP8 mice in accordance with hepatic lipid accumulation. Prevented hepatic lipid accumulation was mainly attributed to inhibited SREBP1c gene expression by EGCG. Ultimately, EGCG supplementation is potential to counteract age‐related metabolic disorders.