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.