Abstract P3132: High-salt Diet Increases Blood Cholesterol: Potential Role Of Hepatic Enzyme CYP51

Abstract

Introduction: The increased consumption of dietary fat has been well established to lead to cardiovascular disease via the elevation of lipids in serum. High blood pressure is also commonly associated with high serum cholesterol levels, but the relationships among blood pressure, dietary sodium intake and serum cholesterol have not been fully elucidated. Hypothesis: An increase in the intake of salt causes an elevation of serum cholesterol through the activation of hepatic enzymes critical to cholesterol synthesis. Methods: Dahl salt-sensitive rats (n=6) were fed a high-salt (HS) diet (8% NaCl) from 7 weeks of age to induce hypertension. Rats fed a normal-salt (NS) diet (0.3% NaCl; n=6) served as controls. Blood pressure was measured non-invasively using a tail artery cuff. Blood was withdrawn from 6-hour fasting HS and NS-fed rats to check serum cholesterol levels. Low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low density lipoprotein (VLDL) cholesterols were measured. Gene expression array and western blot were performed in liver protein extracts from HS and NS-fed rats. Results: Systolic blood pressure was elevated in HS-fed rats compared to NS-fed rats at 16 weeks of age (225±23 vs. 156±18 mmHg, p=0.0002). Serum fasting cholesterol was higher in hypertensive rats compared to normotensive rats (194±49 vs. 102±12 mg/dL, p=0.0013). LDL cholesterol was higher in HS-fed rats compared to NS-fed rats (83±9 vs. 60±10 mg/dL, p=0.0024), while HDL and VLDL cholesterol were not. Hepatic cholesterol synthesis gene array revealed significant up-regulation of 3 genes in hypertensive rats in comparison to normotensive rats ( Apoa1 fold change [FC] 2.84, p<0.0001; Tm7sf2 FC 2.45, p=0.0004; Cyp51 FC 2.44, p=0.0002). Western blot of hepatic protein extracts showed a definitive increase in CYP51 in HS-fed rats compared to NS-fed rats (normalized against GAPDH, 2.7-fold increase, p=0.0018). Conclusions: A high-salt diet increased serum cholesterol levels, potentially via activation of liver enzyme CYP51, which is crucial for the synthesis of cholesterol in the liver. Further research is warranted to investigate the mechanisms of how high-salt diets can increase CYP51 in the liver.