Mogrol Derived from Siraitia grosvenorii Mogrosides Suppresses 3T3-L1 Adipocyte Differentiation by Reducing cAMP-Response Element-Binding Protein Phosphorylation and Increasing AMP-Activated Protein Kinase Phosphorylation

PLoS One. 2016 Sep 1;11(9):e0162252. doi: 10.1371/journal.pone.0162252. eCollection 2016.

Abstract

This study investigated the effects of mogrol, an aglycone of mogrosides from Siraitia grosvenorii, on adipogenesis in 3T3-L1 preadipocytes. Mogrol, but not mogrosides, suppressed triglyceride accumulation by affecting early (days 0-2) and late (days 4-8), but not middle (days 2-4), differentiation stages. At the late stage, mogrol increased AMP-activated protein kinase (AMPK) phosphorylation and reduced glycerol-3-phosphate dehydrogenase activity. At the early stage, mogrol promoted AMPK phosphorylation, inhibited the induction of CCAAT/enhancer-binding protein β (C/EBPβ; a master regulator of adipogenesis), and reduced 3T3-L1 cell contents (e.g., clonal expansion). In addition, mogrol, but not the AMPK activator AICAR, suppressed the phosphorylation and activity of the cAMP response element-binding protein (CREB), which regulates C/EBPβ expression. These results indicated that mogrol suppressed adipogenesis by reducing CREB activation in the initial stage of cell differentiation and by activating AMPK signaling in both the early and late stages of this process.

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Animals
  • Cell Differentiation / drug effects*
  • Cucurbitaceae / chemistry*
  • Cyclic AMP Response Element-Binding Protein / antagonists & inhibitors*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Lipid Metabolism
  • Mice
  • Phosphorylation
  • Signal Transduction
  • Triterpenes / pharmacology*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Triterpenes
  • AMP-Activated Protein Kinases

Grant support

This work was funded by the Japan Society for the Promotion of Science, grant numbers: 20580140 and 15H02900, https://kaken.nii.ac.jp/ja/index (HI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder Saraya Company Ltd. provided support in the form of salaries for authors YI, HT, and YAS, but did not have any role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contribution’ section.