Curcumin induces the expression of carnitine palmitoyltransferase-1A and peroxisome proliferators-activated receptor-alpha on hepatic tissue in acute hyperlipidemic rats

Abstract

Objective To investigate the effects of curcumin on peroxisome proliferators-activated receptor-alpha (PPAR-α)/carnitine palmitoyltransferase-1A (CPT-1A) signal pathway and lipid metabolism in hepatic tissue of acute hyperlipidemic rat, and elucidate the possible mechanisms. Methods The 5-6 week-old male SD rats were randomly divided into 6 groups: normal control group (NC, n=8), acute hyperlipidemia model group (Model, n=8), low-dose curcumin group (LC, 125 mg·kg-1·d-1, n=8), medium-dose curcumin group(MC, 250 mg·kg-1·d-1, n=8), high-dose curcumin group (HC, 500 mg·kg-1·d-1, n=8), and fenofibrate group (FF, 30 mg·kg-1·d-1, n=8). NC and Model groups were given gavage with corn oil(5 ml·kg-1·d-1) and the experimental groups (curcumin and fenofibrate) were given gavage with corresponding drug(dissolved by equal volume of corn oil) once daily for 10 days. Model, curcumin and FF group were injected intraperitoneally with 75% fresh egg yolk emulsion (25 ml/kg) to set up acute hyperlipidemia models (NC group rats were injected with equal volume of saline). After 24 h, blood samples were collected to detect the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and free fatty acids (FFA). The content of TG, FFA in hepatic tissue were detected by colorimetric method. Hematoxylin and eosin (HE) and oil red O staining were adopted to determine the morphological changes and fat mass of the hepatic tissue. The mRNA and protein expressions of PPAR-α, CPT-1A were detected with real-time polymerase chain reaction (PCR) and Western blotting methods. One-way analysis of variance was used when data were compared among multiple groups, and LSD test was applied when data were compared between two groups. Results The blood levels of TG and FFA, hepatic contents of TG and FFA in LC/MC/HC groups decreased significantly than those in model group (t=2.196-27.350, all P<0.05); the swelling and vacuoles of the liver cell lessened and the proportion of lipid droplets reduced. The expression of PPAR-α and CPT-1A mRNA in Model group (0.009±0.003, 0.048±0.012) were both lower than those in NC group (0.022±0.003, 0.086±0.003) (t=-2.862, -30.262, both P<0.05), but the expressions were increased in curcumin groups than those in Model group (t=-22.870--5.509, all P<0.01). The protein expression of PPAR-α and CPT-1A in Model group (0.64±0.05, 0.128±0.012) were lower than those in NC group (0.98±0.09, 0.186±0.018) (t=-2.905--4.145, both P<0.05), but those were increased in curcumin groups (HC, MC, LC group) in a dose-dependent manner than those in Model group (t=-31.065--6.571, all P<0.01). Conclusion Curcumin can reduce serum lipid, improve liver lipid metabolism, thereby protect liver via up-regulating the PPAR-α/CPT-1A pathway. Key words: Curcumin; Hyperlipdemia; Carnitine palmitoyltransferase-1A; Peroxisome proliferators-activated receptor-alpha; Fatty acid oxidation