Which lipid-lowering agent reduces hepatic VLDL secretion and can raise HDL?

• A. Statin
• B. Ezetimibe
• C. Fenofibrate
• D. Niacin

Answer: (D)

Niacin lowers hepatic VLDL secretion by acting on adipose tissue to reduce the release of free fatty acids. When fewer free fatty acids reach the liver, triglyceride synthesis in the liver falls, leading to decreased VLDL production and secretion. Because VLDL is a major precursor to LDL, this also helps reduce LDL levels. In addition, niacin raises HDL cholesterol, in part by decreasing the clearance of HDL particles and promoting HDL formation, so HDL levels increase.

Other agents work by different mechanisms: statins inhibit hepatic cholesterol synthesis and upregulate LDL receptors to lower LDL; ezetimibe blocks intestinal cholesterol absorption; fibrates (like fenofibrate) activate PPAR-alpha to boost fatty acid oxidation and LPL activity, lowering triglycerides and often modestly increasing HDL, but they do not target hepatic VLDL secretion as specifically as niacin.