Wnt5a regulates the cell proliferation and adipogenesis via MAPK-independent pathway in early stage of obesity

Cell Biol Int. 2018 Jan;42(1):63-74. doi: 10.1002/cbin.10862. Epub 2017 Oct 16.

Abstract

The early stage of obesity is an important stage in the development of obesity. However, there are few studies which explored the property or changes in obesity at early stage especially involving Wnt5a. The associated gene expression of Wnt5a on cell regeneration and the effect of Wnt5a on rat adipose-derived stem cell (rASC) proliferation and adipogenesis need additional study. Here, we investigated the changes in obesity at early stage and how Wnt5a regulates rASC regeneration, proliferation, and adipogenesis. Our data revealed that obesity at early stage measured by Lee index presented a state with impaired adipogenesis and more infiltrated inflammatory cells but without significant changes in adipocyte sizes and inflammatory factors. The process might be associated with anti-canonical Wnt pathway and a reciprocal Wnt5a/JNK pathway. Besides the gene expression of Wnt5a decreased from cell passage 1 to passage 3. The cell proliferation was regulated by increasing dose of Wnt5a with the maximal effect at 50 ng/mL and 50 ng/mL Wnt5a suppressed adipogenic differentiation at middle-late stage of adipogenesis via anti-β-catenin and a mitogen-activated protein kinase (MAPK) signaling-independent manner. Accordingly, the research helps to gain further insights into the early stage of obesity and its associated changes on a cellular and molecular level.

Keywords: JNK signaling pathway; Wnt5a; adipogenesis; adipose-derived stem cell (ASC); obesity; β-catenin pathway.

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adipogenesis / physiology*
  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Diet, High-Fat
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Obesity / metabolism*
  • Obesity / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Wnt Signaling Pathway
  • Wnt-5a Protein / metabolism*
  • Wnt-5a Protein / pharmacology

Substances

  • Wnt-5a Protein
  • Wnt5a protein, rat
  • Mitogen-Activated Protein Kinases