Pronuciferine and nuciferine inhibit lipogenesis in 3T3-L1 adipocytes by activating the AMPK signaling pathway

Life Sci. 2015 Sep 1:136:120-5. doi: 10.1016/j.lfs.2015.07.001. Epub 2015 Jul 9.

Abstract

Aims: Nelumbo nucifera (Gaertn.) leaves are used widely in modulating obesity in traditional Chinese medicine. Our previous work demonstrated that aporphine alkaloids from it increased the glucose consumption in mature 3T3-L1 adipocytes. However, the underlying mechanisms of this increase remain unclear. Here we investigated the modulating effects of pronuciferine and nuciferine on lipogenesis and glucose uptake in insulin resistant 3T3-L1 adipocytes in vitro.

Main methods: Insulin resistant 3T3-L1 mature adipocytes were induced with dexamethasone, 3-isobutyl-methylxanthine and insulin. The lipid droplets and the intracellular triglyceride contents in mature adipocytes were detected by Oil red O staining and colorimetry respectively. The glucose uptake was measured with a fluorescent deoxyglucose analog (2-NBDG). The glucose transporter type 4 (GLUT-4) expression was measured by fluorescent-immunohistochemistry and the activation of 5'-AMP-activated protein kinase (AMPK) was detected by its alpha subunit phosphorylation.

Key findings: Both nuciferine and pronuciferine treatments significantly decreased the lipid droplets and the intracellular triglyceride contents but increased the glucose uptake in the insulin resistant 3T3-L1 adipocytes. Furthermore, both pronuciferine and nuciferine showed the ability to up-regulate the expression of GLUT4, triggering the phosphorylation of AMPK in mature 3T3-L1 adipocytes, although pronuciferine exhibited a more powerful effect compared to nuciferine.

Significance: In summary, all the results demonstrate that pronuciferine and nuciferine ameliorate the glucose and lipid metabolism in insulin-resistant 3T3-L1 adipocytes, which might be due to the activation of the AMPK signaling pathway.

Keywords: 3T3-L1 adipocytes; AMPK; Lipogenesis; Nuciferine; Pronuciferine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • AMP-Activated Protein Kinases / metabolism
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Anti-Obesity Agents / pharmacology*
  • Aporphines / pharmacology*
  • Drug Evaluation, Preclinical
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Lipid Droplets / metabolism
  • Lipogenesis / drug effects*
  • Mice
  • Signal Transduction / drug effects*
  • Spiro Compounds / pharmacology*

Substances

  • Anti-Obesity Agents
  • Aporphines
  • Glucose Transporter Type 4
  • Slc2a4 protein, mouse
  • Spiro Compounds
  • pronuciferine
  • AMP-Activated Protein Kinases
  • Glucose
  • nuciferine