The anti-obesity effects of a tuna peptide on 3T3-L1 adipocytes are mediated by the inhibition of the expression of lipogenic and adipogenic genes and by the activation of the Wnt/β-catenin signaling pathway

Int J Mol Med. 2015 Aug;36(2):327-34. doi: 10.3892/ijmm.2015.2231. Epub 2015 Jun 3.


The differentiation of 3T3-L1 cells into adipocytes involves the activation of an organized system of obesity-related genes, of which those encoding CCAAT/enhancer-binding proteins (C/EBPs) and the Wnt-10b protein may play integral roles. In a previous study of ours, we found that a specific peptide found in tuna (sequence D-I-V-D-K-I-E-I; termed TP-D) inhibited 3T3-L1 cell differentiation. In the present study, we observed that the expression of expression of C/EBPs and Wnt-10b was associated with obesity. The initial step of 3T3-L1 cell differentiation involved the upregulation of C/EBP-α expression, which in turn activated various subfactors. An upstream effector of glycogen synthase kinase-3β (GSK-3β) inhibited Wnt-10b expression in 3T3-L1 adipocytes. In a previous study of ours, we sequenced the tuna peptide via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and quadrupole time-of-flight mass spectrometry (Q-TOF MS/MS) and confirmed the anti-obesity effects thereof in 3T3-L1 adipocytes. In the present study, we demonstrate that TP-D inhibits C/EBP and promotes Wnt-10b mRNA expression, thus activating the Wnt pathway. The inhibition of lipid accumulation was measured using a glucose and triglyceride (TG) assay. Our results confirmed that TP-D altered the expression levels of C/EBP-related genes in a dose-dependent manner and activated the Wnt signaling pathway. In addition, we confirmed that total adiponectin and high-molecular weight (HMW) adiponectin levels were reduced by treatment with TP-D. These data indicate that TP-D inhibits adipocyte differentiation through the inhibition of C/EBP genes and the subsequent activation of the Wnt/β-catenin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Adiponectin / metabolism
  • Amino Acid Sequence
  • Animals
  • Anti-Obesity Agents / chemistry
  • Anti-Obesity Agents / pharmacology*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects*
  • Glucose / metabolism
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Lipogenesis / drug effects
  • Mice
  • Obesity / drug therapy
  • Obesity / genetics
  • Obesity / metabolism
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Triglycerides / metabolism
  • Tuna / metabolism
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / drug effects*


  • Adiponectin
  • Anti-Obesity Agents
  • CCAAT-Enhancer-Binding Proteins
  • Peptides
  • Triglycerides
  • Wnt Proteins
  • Wnt10b protein, mouse
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, mouse
  • Glycogen Synthase Kinase 3
  • Glucose