Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet

Food Funct. 2018 Apr 25;9(4):2043-2050. doi: 10.1039/C7FO01817G.

Abstract

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 μM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / chemistry
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes, Beige / drug effects
  • Adipocytes, Beige / metabolism*
  • Adipocytes, Beige / pathology
  • Adipogenesis / drug effects
  • Adiposity
  • Animals
  • Anti-Obesity Agents / antagonists & inhibitors
  • Anti-Obesity Agents / metabolism
  • Anti-Obesity Agents / therapeutic use*
  • Biomarkers / metabolism
  • Diet, High-Fat / adverse effects
  • Dietary Supplements*
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / prevention & control*
  • Phytol / antagonists & inhibitors
  • Phytol / metabolism
  • Phytol / therapeutic use*
  • Protein Kinase Inhibitors / pharmacology
  • Random Allocation
  • Signal Transduction / drug effects
  • Subcutaneous Fat, Abdominal / drug effects
  • Subcutaneous Fat, Abdominal / metabolism*
  • Subcutaneous Fat, Abdominal / pathology

Substances

  • Anti-Obesity Agents
  • Biomarkers
  • Protein Kinase Inhibitors
  • Phytol
  • AMP-Activated Protein Kinases