Suppression of Fatty Acid and Triglyceride Synthesis by the Flavonoid Orientin through Decrease of C/EBPδ Expression and Inhibition of PI3K/Akt-FOXO1 Signaling in Adipocytes

Nutrients. 2018 Jan 26;10(2):130. doi: 10.3390/nu10020130.

Abstract

Plant flavonoids have a variety of biological properties. In a previous study, we found that the tea of the Asian dayflower, Commelina communis L., decreased the body weight gain in high-fat diet-fed mice. In this study, we studied the anti-adipogenic ability of a flavonoid orientin that is found in abundance in C. communis. Orientin repressed the accumulation of intracellular triglyceride (TG) in mouse adipocyte 3T3-L1 cells. The treatment with orientin also decreased the mRNA levels of the genes involved in adipogenesis, lipogenesis, lipolysis, and TG synthesis, and reduced the release of glycerol. Orientin lowered the expression of CCAAT/enhancer binding protein (C/EBP) δ in the early stage of adipogenesis, leading to a decrease in the expression of the adipogenic master transcription factors such as peroxisome proliferator-activated receptor (PPAR) γ and C/EBPα. Moreover, the anti-adipogenic effect of orientin repressed the phosphorylation of Akt and subsequent phosphorylation of forkhead box protein O1 (FOXO1), which inhibits the transcription of the Ppar gene. These results indicate that a plant flavonoid orientin suppressed the expression of the Pparγ gene through repression of C/ebpδ expression and inhibition of the phosphoinositide 3-kinase /Akt-FOXO1 signaling in adipocytes.

Keywords: C/EBPδ; FOXO1; PI3K/Akt; adipogenesis; orientin.

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases / antagonists & inhibitors
  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism
  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / enzymology
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • CCAAT-Enhancer-Binding Protein-delta / antagonists & inhibitors*
  • CCAAT-Enhancer-Binding Protein-delta / genetics
  • CCAAT-Enhancer-Binding Protein-delta / metabolism
  • CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Flavonoids / pharmacology*
  • Forkhead Box Protein O1 / antagonists & inhibitors
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Regulation, Developmental / drug effects*
  • Glucosides / pharmacology*
  • Glycerol / metabolism
  • Lipolysis / drug effects
  • Mice
  • PPAR gamma / antagonists & inhibitors*
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Triglycerides / metabolism

Substances

  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, mouse
  • Cebpd protein, mouse
  • Flavonoids
  • Forkhead Box Protein O1
  • Foxo1 protein, mouse
  • Glucosides
  • PPAR gamma
  • Triglycerides
  • CCAAT-Enhancer-Binding Protein-delta
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Proto-Oncogene Proteins c-akt
  • orientin
  • Glycerol