Curcumin inhibits hepatic protein-tyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats

Hepatology. 2010 May;51(5):1555-66. doi: 10.1002/hep.23524.


High consumption of dietary fructose is an important contributory factor in the development of hepatic steatosis in insulin or leptin resistance. We investigated the effects of curcumin on fructose-induced hypertriglyceridemia and liver steatosis and explored its preventive mechanisms in rats. Curcumin reduced serum insulin and leptin levels in fructose-fed rats. This compound could increase phosphorylation of insulin receptor and insulin receptor substrate 1 to enhance Akt and extracellular signal-regulated kinase1/2 (ERK1/2) activation in the liver of fructose-fed rats. Moreover, curcumin increased phosphorylation of hepatic janus-activated kinase-signal transducer 2 and subsequently also stimulated Akt and ERK1/2 activation in this model. Suppression of curcumin on leptin signaling overstimulation in tyrosine1138 phosphorylation of the long form of leptin receptor and signal transducer and activator of transcription 3 resulted in down-regulation of suppressor of cytokine signaling 3 in the liver of fructose-fed rats. Thus, improvement of insulin and leptin signaling transduction and subsequently elevation of peroxisome proliferator-activated receptor alpha expression by curcumin led to reduction of very-low-density lipoprotein overproduction and triglyceride hypersynthesis. Furthermore, overexpression and hyperactivity of hepatic protein tyrosine phosphatase 1B (PTP1B) associated with defective insulin and leptin signaling were observed in fructose-fed rats. Additionally, curcumin was found to significantly reduce hepatic PTP1B expression and activity in this model.

Conclusion: Our data indicate that the mechanisms by which curcumin protects against fructose-induced hypertriglyceridemia and hepatic steatosis are its inhibition on PTP1B and subsequently improvement of insulin and leptin sensitivity in the liver of rats. This PTP1B inhibitory property may be a promising therapeutic strategy for curcumin to treat fructose-induced hepatic steatosis driven by hepatic insulin and leptin resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Curcumin / pharmacology*
  • Dietary Carbohydrates / administration & dosage
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Fatty Liver / prevention & control*
  • Fructose / administration & dosage
  • Fructose / pharmacology*
  • Hypertriglyceridemia / prevention & control*
  • Insulin Resistance / physiology
  • Leptin / blood
  • Liver / drug effects
  • Male
  • Pioglitazone
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Thiazolidinediones / pharmacology


  • Dietary Carbohydrates
  • Leptin
  • Thiazolidinediones
  • Fructose
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Curcumin
  • Pioglitazone