Attenuation of hepatic steatosis by purple sweet potato colour is associated with blocking Src/ERK/C/EBPβ signalling in high-fat-diet-treated mice

Appl Physiol Nutr Metab. 2017 Oct;42(10):1082-1091. doi: 10.1139/apnm-2016-0635. Epub 2017 Jun 21.

Abstract

Our previous work showed that purple sweet potato colour (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat-diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into 4 groups: control group, HFD group, HFD+PSPC group, and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/(kg·day)-1). Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice. Moreover, PSPC dramatically attenuated hepatic steatosis in HFD-treated mice. PSPC markedly prevented oxidative stress-mediated Src activation in HFD-treated mouse livers. Furthermore, PSPC feeding remarkably suppressed mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) signalling and consequent CCAAT/enhancer binding protein β (C/EBPβ) activation and restored AMPK activation in HFD-treated mouse livers, which was confirmed by U0126 treatment. Ultimately, PSPC feeding dramatically reduced protein expression of FAS and CD36 and the activation of ACC, and increased the protein expression of CPT1A in the livers of HFD-treated mice, indicating decreased lipogenesis and fatty acid uptake and enhanced fatty acid oxidation. In conclusion, PSPC exhibited beneficial effects on hepatic steatosis, which were associated with blocking Src and C/EBPβ activation.

Keywords: CCAAT/enhancer binding protein β; CCAAT/renforcement de la protéine de liaison β; Src; alimentation riche en gras; couleur de patate douce pourpre; extracellular-signal-regulated kinase; hepatic steatosis; high-fat diet; kinase régulée par un signal extracellulaire; oxidative stress; purple sweet potato color; stress oxydatif; stéatose hépatique.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Anthocyanins / isolation & purification
  • Anthocyanins / pharmacology*
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • CD36 Antigens / metabolism
  • Diet, High-Fat*
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Enzyme Activation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Ipomoea batatas* / chemistry
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Male
  • Mice, Inbred ICR
  • Non-alcoholic Fatty Liver Disease / enzymology
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Obesity / enzymology
  • Obesity / pathology
  • Obesity / prevention & control
  • Oxidative Stress / drug effects
  • Phytotherapy
  • Pigments, Biological / isolation & purification
  • Pigments, Biological / pharmacology*
  • Plants, Medicinal
  • Signal Transduction / drug effects
  • Time Factors
  • fas Receptor / metabolism
  • src-Family Kinases / metabolism*

Substances

  • Anthocyanins
  • CCAAT-Enhancer-Binding Protein-beta
  • CD36 Antigens
  • Cebpb protein, mouse
  • Fas protein, mouse
  • Pigments, Biological
  • fas Receptor
  • src-Family Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase