Indirubin promotes adipocyte differentiation and reduces lipid accumulation in 3T3‑L1 cells via peroxisome proliferator‑activated receptor γ activation

Mol Med Rep. 2020 Mar;21(3):1552-1560. doi: 10.3892/mmr.2020.10946. Epub 2020 Jan 16.

Abstract

The peroxisome proliferator‑activated receptor γ (PPARγ) plays an important role in insulin sensitivity and adipocyte differentiation. It is known as ligand‑receptor that improves insulin sensitivity in type 2 diabetes mellitus. Several kinds of indigo plant have been already used to treat diabetes in oriental traditional medicine, but its mechanism has not been clarified yet. To investigate the effect of indirubin, which is a component of Polygonum tinctorium on the cell differentiation and adipprocess in 3T3‑L1 cells, 3T3‑L1 cells were cultured to determine the effect of cell differentiation and glucose uptake with indirubin. As a result, Indirubin compound enhanced adipocyte differentiation in 3T3‑L1 cells similar to rosiglitazone. This effect was terminated by cotreatment with GW9662, a PPARγ antagonist. In mature 3T3‑L1 adipocytes, the lipid droplet size and accumulation were reduced by this compound. The basal and insulin‑stimulated glucose uptakes were also significantly increased. In addition, indirubin treatment significantly enhanced estrogen level by 1.64‑fold with mature adipocytes which can be attributed to its aromatase activity. Conclutionaly, this finding suggested that indirubin is a potential anti‑diabetic compound for type 2 diabetes mellitus by promoting adipocyte differentiation and glucose uptake via PPARγ.

Keywords: indirubin; polygonum tinctorium; insulin resistance; diabetes mellitus; PPARγ; 3T3‑L1 cells; lipid accumulation; glucose uptake; estrogen.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipocytes / metabolism*
  • Animals
  • Biomarkers
  • Cell Differentiation / drug effects*
  • Cell Proliferation
  • Glucose / metabolism
  • Hypoglycemic Agents / pharmacology
  • Indoles / pharmacology
  • Insulin / metabolism
  • Ligands
  • Lipid Metabolism / drug effects*
  • Mice
  • PPAR gamma / metabolism*
  • Protein Kinase Inhibitors / pharmacology*
  • Rosiglitazone / pharmacology

Substances

  • Biomarkers
  • Hypoglycemic Agents
  • Indoles
  • Insulin
  • Ligands
  • PPAR gamma
  • Protein Kinase Inhibitors
  • Rosiglitazone
  • Glucose
  • indirubin