UNLABELLED: 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.
UNLABELLED: 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.
Authors: Samir Softic; Kimber L Stanhope; Jeremie Boucher; Senad Divanovic; Miguel A Lanaspa; Richard J Johnson; C Ronald Kahn Journal: Crit Rev Clin Lab Sci Date: 2020-01-14 Impact factor: 6.250
Authors: Ganesan Murali; Ginger L Milne; Corey D Webb; Ann B Stewart; Ryan P McMillan; Brandon C Lyle; Matthew W Hulver; Viswanathan Saraswathi Journal: J Lipid Res Date: 2012-07-29 Impact factor: 5.922