A 36-year-old man comes to the office after he was found to have an abnormal lipid panel during employee wellness testing at his company. He has no prior medical problems and takes no medications. The patient is a software technician and has a sedentary lifestyle. He eats mostly fast foods, rarely exercises, and drinks 2-3 cans of beer daily. His BMI is 31 kg/m². Physical examination is unremarkable. Results of laboratory studies performed in the office are as follows: Lifestyle modification with a balanced diet, regular exercise, and reduced alcohol intake is advised. He is also started on fenofibrate therapy. This medication is most likely to help the patient by which of the following mechanisms?

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11ec160b_3b8b_9f6e_9249_6f2283071fcd_MD0001_00 This patient has a moderately elevated (>500 mg/dL) triglyceride level, which is associated with an increased risk of cardiovascular disease. Lifestyle modifications (increased aerobic exercise, decreased alcohol and total caloric intake) can decrease triglycerides, but moderate (or worse) hypertriglyceridemia usually requires pharmacologic therapy. Lipoprotein lipase (LPL) hydrolyzes triglycerides in chylomicrons and VLDL to release free fatty acids, which can be used for energy or converted back to triglycerides for storage in adipose tissue. It also facilitates the transfer of triglycerides from these lipoproteins to HDL. Fibrates (eg, gemfibrozil, fenofibrate) activate peroxisome proliferator-activated receptor alpha (PPAR-α), which leads to decreased hepatic VLDL production and increased LPL activity. They are able to decrease triglyceride levels by 25%-50% and increase HDL by 5%-20%. Fish oil supplements containing high concentrations of omega-3 fatty acids also decrease VLDL production, and inhibit synthesis of apolipoprotein B as well. These supplements lower triglycerides and can be used as an alternate treatment for patients with moderate hypertriglyceridemia. (Choices A, C, and D) Ezetimibe selectively blocks intestinal cholesterol absorption. Bile acid-binding resins (eg, cholestyramine) increase fecal loss of cholesterol derivatives by binding bile acids in the intestine and disrupting enterohepatic bile acid circulation. Proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are monoclonal antibodies that reduce LDL receptor degradation in the liver. These drugs are used primarily in patients with elevated cholesterol levels but have minimal effect on triglyceride levels. (Choice B) Statins (eg, atorvastatin) decrease hepatic cholesterol synthesis by inhibiting HMG-CoA reductase. Statins have a modest effect on triglyceride levels and are recommended for patients with mild to moderate hypertriglyceridemia. Educational objective: Fibrates lower triglyceride levels by activating peroxisome proliferator-activated receptor alpha, which leads to decreased hepatic VLDL production and increased lipoprotein lipase activity. Fish oil supplements containing high concentrations of omega-3 fatty acids lower triglycerides by decreasing production of VLDL and apolipoprotein B. __________ References: Fenofibrate: a review of its use in dyslipidaemia. (http://www.ncbi.nlm.nih.gov/pubmed/21942979)

A 36-Year-Old Man Comes to the Office After He Was