title: Curcumin inhibits hepatic protein-tyrosine phosphatase 1B and prevents hypertriglyceridemia and hepatic steatosis in fructose-fed rats.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Li
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Hu
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005234:Fatty Liver / Q000517:prevention & control*; D005632:Fructose / Q000008:administration & dosage / Q000494:pharmacology*; D015228:Hypertriglyceridemia / Q000517:prevention & control*; D007333:Insulin Resistance / Q000502:physiology; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects; D008297:Male; D000077205:Pioglitazone; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D004040:Dietary Carbohydrates; D020738:Leptin; D045162:Thiazolidinediones; D005632:Fructose; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D003474:Curcumin; D000077205:Pioglitazone