Curcumin suppresses Notch-1 signaling: Improvements in fatty liver and insulin resistance in rats

Curcumin is a well-known phenolic substance and has many pharmacological effects associated with metabolism. However, the exact molecular mechanisms underlying this process have yet to be determined. The Notch pathway is a signal transduction pathway involved in energy metabolism. The present study aimed to investigate the effects of curcumin administration on glucose-lipid metabolism in rats subjected to a high fat diet, and investigate changes in Notch-1 signaling. Sprague-Dawley rats (n=40) were randomly divided into four groups (10 rats/group): Control diet group, high fat diet group, high fat diet plus curcumin low dose group and high fat diet plus curcumin high dose group. Following 8 weeks of treatment with curcumin (100 mg/kg in the low dose group and 200 mg/kg in the high dose group), serum metabolic markers and hepatic gene expression patterns were investigated. No differences in body weight following 8 weeks of curcumin administration (P>0.05) were observed; however, curcumin treatment did reduce visceral fat levels (peri-epididymal and peri-renal), and decreased cholesterol, triglyceride and low-density lipoprotein levels in serum compared with the high fat diet rats that did not receive curcumin (P<0.05, P<0.01). An oral glucose tolerance test and an intraperitoneal insulin tolerance test revealed that insulin resistance was reduced (P<0.05 or P<0.01) and tissue section analysis revealed that hepatosteatosis was attenuated following treatment with curcumin. Furthermore, the protein expression of Notch-1 and its downstream target Hes-1 were suppressed. These effects were also in parallel with an upregulation of fatty acid oxidation-associated gene expression, including peroxisome proliferator-activated receptor (PPAR)-α, carnitine palmitoyltransferase 1 and PPAR-γ (P<0.05). In addition, curcumin administration led to a downregulation in the expression of lipogenic genes, including sterol regulatory element-binding protein, fatty acid synthase and acetyl-CoA carboxylase (P<0.05). The expression of inflammation-associated genes, including nuclear factor-κB, tumor necrosis factor-α and prostaglandin-endoperoxide synthase 2 were also suppressed. The results of the present study suggest that the hepatic Notch-1 pathway can be suppressed via curcumin treatment, which may ameliorate fatty liver and insulin resistance in rats subjected to a high fat diet.