δ-Tocopherol promotes thermogenic gene expression via PGC-1α upregulation in 3T3-L1 cells

Biochem Biophys Res Commun. 2018 Nov 17;506(1):53-59. doi: 10.1016/j.bbrc.2018.10.021. Epub 2018 Oct 15.

Abstract

Activation of thermogenic adipocytes (brown and beige) has been considered an attractive target for weight loss and treatment of metabolic disease. Peroxisome proliferator-activated receptor γ co-activator-1 α (PGC1-α) is a master regulator of thermogenic gene expression in thermogenic adipocytes. We previously reported that α-tocopherol upregulated PGC-1α gene expression and promoted thermogenic adipocyte differentiation in mammalian adipocytes. In this study, we investigated the effects of the vitamin E analogs (α-, γ- and δ-tocopherol) on PGC-1α and uncoupling protein 1 (UCP1) gene expression in 3T3-L1 cells. The expression of PGC-1α and UCP1 increased significantly with the addition of δ-tocopherol. In δ-tocopherol-treated cells, nuclear translocation of PGC-1α increased, as did p38 mitogen-activated protein kinase (MAPK) expression and phosphorylation. Our results suggest that p38 MAPK activation by δ-tocopherol contributes to PGC-1α activation and UCP1 induction.

Keywords: PGC-1α; Thermogenic adipocytes; Tocopherol; UCP1; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / drug effects*
  • Adipocytes, Brown / metabolism
  • Animals
  • Cell Differentiation
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Gene Expression Regulation
  • Mice
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / agonists
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Signal Transduction
  • Tocopherols / pharmacology*
  • Uncoupling Protein 1 / genetics*
  • Uncoupling Protein 1 / metabolism
  • alpha-Tocopherol / pharmacology
  • gamma-Tocopherol / pharmacology
  • p38 Mitogen-Activated Protein Kinases / genetics*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • gamma-Tocopherol
  • p38 Mitogen-Activated Protein Kinases
  • alpha-Tocopherol
  • delta-tocopherol
  • Tocopherols