Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

Oncotarget. 2015 Oct 13;6(31):30568-78. doi: 10.18632/oncotarget.5215.

Abstract

In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

Keywords: Drosophila melanogaster; Gerotarget; epigallocathechin-3-gallate; green tea; life span.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Camellia sinensis / metabolism
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Drosophila Proteins / biosynthesis
  • Drosophila melanogaster / metabolism
  • Energy Metabolism / drug effects*
  • Glucose / metabolism*
  • Homeostasis / drug effects
  • Insulin / biosynthesis
  • Longevity / drug effects
  • Longevity / physiology*
  • Molecular Docking Simulation
  • Phosphoenolpyruvate Carboxykinase (ATP) / biosynthesis
  • Plant Extracts / pharmacology
  • Positive Transcriptional Elongation Factor B / biosynthesis
  • Proteins
  • Transcription Factors / biosynthesis
  • Up-Regulation
  • alpha-Amylases / metabolism
  • alpha-Glucosidases / metabolism

Substances

  • Antioxidants
  • Drosophila Proteins
  • Insulin
  • Leydig insulin-like protein
  • Plant Extracts
  • Proteins
  • Transcription Factors
  • pgc protein, Drosophila
  • upd1 protein, Drosophila
  • Catechin
  • epigallocatechin gallate
  • Positive Transcriptional Elongation Factor B
  • alpha-Amylases
  • alpha-Glucosidases
  • Phosphoenolpyruvate Carboxykinase (ATP)
  • Glucose