Development of insulin resistance through sprouting of inflammatory markers during hypoxia in 3T3-L1 adipocytes and amelioration with curcumin

Eur J Pharmacol. 2017 Oct 5:812:73-81. doi: 10.1016/j.ejphar.2017.07.005. Epub 2017 Jul 4.

Abstract

The role of phytochemicals in general well-being has been recognized. Curcumin is an ideal example. Hypoxia in adipose tissue is a major cause of inflammation and insulin resistance in obesity. Herein we mainly explored inflammation, insulin resistance and angiogenesis in 3T3-L1 adipocytes and possible reversal with the curcumin during hypoxia. Hypoxia for 24h significantly increased (P ≤ 0.05) the secretion of monocyte chemotactic protein-1 (4.59 fold), leptin (2.96 fold) and reduced adiponectin (2.93 fold). mRNA level of resistin (6.8 fold) and toll-like receptor-4 (TLR-4) (8.8 fold) was upregulated. Increased serine phosphorylation of insulin receptor substrate 1 (IRS-1) (1.9 fold) and decreased expression of insulin receptor substrate 2 (IRS-2) (0.53 fold) in hypoxic group were observed. Hypoxia significantly increased (P ≤ 0.05) basal glucose uptake (3.3 fold), GLUT-1 expression and angiogenic factors but down regulated GLUT-4. Curcumin protected adipocytes from hypoxia induced inflammation and insulin resistance via reducing inflammatory adipokine, nuclear factor-κB (NF-κB)/c-jun N-terminal kinase (JNK) and serine phosphorylation of IRS-1 receptors and improving adiponectin secretion.

Keywords: 3T3-L1 adipocytes; Curcumin; Hypoxia; Inflammation; Insulin resistance.

MeSH terms

  • 3T3-L1 Cells
  • Active Transport, Cell Nucleus / drug effects
  • Adipocytes / cytology*
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Animals
  • Biomarkers / metabolism
  • Cell Hypoxia / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Curcumin / pharmacology*
  • Cytokines / metabolism
  • Enzyme Activation / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose Transporter Type 1 / metabolism
  • Insulin Resistance*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Mice
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Glucose Transporter Type 1
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • JNK Mitogen-Activated Protein Kinases
  • Curcumin