Promoting Effect of α-Tocopherol on Beige Adipocyte Differentiation in 3T3-L1 Cells and Rat White Adipose Tissue

J Oleo Sci. 2017;66(2):171-179. doi: 10.5650/jos.ess16137.

Abstract

Thermogenic adipocytes that are distinct from classical brown adipocytes (beige adipocytes) were identified in 2012. Beige adipocytes are also called inducible brown adipocytes because their differentiation is induced by a number of physiological stimuli, including adrenaline or myokines. PPARγ is the master regulator of adipogenesis and promotes thermogenic adipocyte differentiation. A PPARγ agonist also promotes thermogenic adipocyte differentiation in mouse white adipose tissues. The vitamin E analog α-tocopherol promotes PPARγ expression and induces mRNA expression of target genes. This study investigated the effects of vitamin E analogs on thermogenic adipocyte differentiation in mouse preadipocytes and rat white adipose tissues. We determined the effects of vitamin E analogs (α-tocopherol and γ-tocopherol) on PPARγ, PGC-1α, and uncoupling protein 1 (UCP1) gene expression in 3T3-L1 cells. UCP1 expression and the mitochondrial contents were confirmed in the cells using immunofluorescence. In an in vivo study, male SD-IGS rats were fed a high-fat diet (HFD), α-tocopherol-enriched HFD, or γ-tocopherol-enriched HFD for 8 weeks before the analysis of PPARγ, PGC-1α, UCP1, and CD137 gene expression, and pathological examinations of white adipose tissues. The expression of PPARγ, PGC-1α, and UCP1 increased in 3T3-L1 cells following α-tocopherol treatment in a concentration-dependent manner. UCP1 expression and mitochondrial content also increased in α-tocopherol-treated cells. According to the histopathological examinations of rat white adipose tissues, multilocular cells were observed in the α-tocopherol intake group. Furthermore, the gene expression levels of PGC-1α, UCP1, and CD137 increased in the α-tocopherol intake group. Our results suggest that α-tocopherol promotes thermogenic adipocyte differentiation in mammalian white adipose tissues.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes, Beige / cytology*
  • Adipocytes, Beige / drug effects*
  • Adipose Tissue, White / cytology*
  • Adipose Tissue, White / drug effects*
  • Animals
  • Body Weight / drug effects
  • Cell Differentiation / drug effects*
  • Cells, Cultured
  • Diet, High-Fat
  • Dose-Response Relationship, Drug
  • Male
  • Mice
  • PPAR gamma / genetics
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • RNA, Messenger / drug effects
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Uncoupling Protein 1 / genetics
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / pharmacology*

Substances

  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • RNA, Messenger
  • Ucp1 protein, rat
  • Uncoupling Protein 1
  • alpha-Tocopherol