Dietary Garcinol Attenuates Hepatic Pyruvate and Triglyceride Accumulation by Inhibiting P300/CBP-Associated Factor in Mid-to-Late Pregnant Rats.

ABSTRACT

BACKGROUND: Increased hepatic glycolysis and lipogenesis are characteristic of pregnancy. OBJECTIVES: The present study aimed to investigate the mechanism of garcinol on the amelioration of hepatic pyruvate and triglyceride (TG) accumulation in mid-to-late pregnant rats. METHODS: Forty Sprague-Dawley pregnant rats (aged 9 wk, n = 10/diet) were fed a basal diet (control) or that diet plus garcinol at 100 ppm (Low Gar), 300 ppm (Mid Gar), or 500 ppm (High Gar) for 14 d. The livers were processed for Western blotting analyses and measuring enzymatic activity and pyruvate and TG concentrations. Hepatocytes from other pregnant Sprague Dawley rats were transfected with P300/CBP associating factor (PCAF) short interfering (si)RNAs; hepatocytes from nonpregnant Sprague-Dawley rats with overexpression of PCAF were treated with garcinol (5 µM). The activity and acetylation of upstream stimulatory factor (USF-1) and glycolytic enzymes were analyzed. RESULTS: Dietary garcinol significantly decreased (P < 0.05) concentrations of hepatic and plasma TG (27.1-45.8%) and total cholesterol (25.3-49.5%), plasma free fatty acids (24.4-37.8%), and hepatic pyruvate (31.5-43.5%) and lactate (33.4-65.7%) in mid-to-late pregnant rats. Garcinol promoted (P < 0.05) antioxidant capacity in the liver and plasma by 27.4-32.1%. Garcinol downregulated (P < 0.05) lipid synthesis-related enzyme expression by 30.6-85.3% and decreased (P < 0.05) glycolytic enzyme activities by 22.5-74.6% and PCAF activity by 18.6-55.4%. Transfection of PCAF siRNAs to hepatocytes of pregnant rats decreased USF-1 and glycolytic enzyme activities by PCAF; garcinol treatment downregulated (P < 0.05) the acetylation and activities of USF-1 and glycolytic enzymes by 35.6-83.7%. CONCLUSIONS: Garcinol attenuates hepatic pyruvate and TG accumulation in the liver of mid-to-late pregnant rats, which may be due to downregulating the acetylation of USF-1 and the glycolytic enzymes induced by PCAF in isolated hepatocytes.