Effect of Fenofibrate and Niacin on Intrahepatic Triglyceride Content, Very Low-Density Lipoprotein Kinetics, and Insulin Action in Obese Subjects with Nonalcoholic Fatty Liver Disease

• Published in: The journal of clinical endocrinology and metabolism Vol. 95; no. 6; pp. 2727 - 2735
• Main Authors: Fabbrini, Elisa, Mohammed, B. Selma, Korenblat, Kevin M., Magkos, Faidon, McCrea, Jennifer, Patterson, Bruce W., Klein, Samuel
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.2010; Copyright by The Endocrine Society; Endocrine Society; The Endocrine Society
• Subjects: Adipose tissue; Adult; Apolipoprotein B; Apolipoproteins; Apolipoproteins B - metabolism; Biological and medical sciences; Blood Glucose - metabolism; Body Composition - drug effects; Body mass index; Cardiovascular diseases; Disease resistance; Double-Blind Method; Endocrinopathies; Fatty acids; Fatty Acids, Nonesterified - blood; Fatty liver; Fatty Liver - complications; Fatty Liver - drug therapy; Fatty Liver - metabolism; Feeding. Feeding behavior; Female; Fenofibrate; Fenofibrate - therapeutic use; Fundamental and applied biological sciences. Psychology; Glucose Clamp Technique; Humans; Hypertriglyceridemia; Hypolipidemic Agents - therapeutic use; Insulin - physiology; Insulin Resistance; Kinetics; Lipoproteins (very low density); Lipoproteins, VLDL - metabolism; Liver - drug effects; Liver - metabolism; Liver diseases; Male; Medical sciences; Middle Aged; Niacin - therapeutic use; Nicotinic acid; Obesity - complications; Obesity - drug therapy; Obesity - metabolism; Original; Plasma; Risk Factors; Secretion; Triglycerides - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Obesity; Pancreatic hormone; Lipoprotein VLDL; Nutrition; Fibrate derivatives; Nutrition disorder; Nicotinic acid; Lipids; Hepatic disease; Metabolic diseases; B-Vitamins; Triglyceride; Insulin; Pyridine derivatives; Fenofibrate; Non alcoholic steatohepatitis; Content; Digestive diseases; Kinetics; Intrahepatic; Endocrinology; Nutritional status; Antilipemic agent
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2009-2622

Context: Nonalcoholic fatty liver disease is associated with risk factors for cardiovascular disease, particularly increased plasma triglyceride (TG) concentrations and insulin resistance. Fenofibrate and extended release nicotinic acid (Niaspan) are used to treat hypertriglyceridemia and can affect fatty acid oxidation and plasma free fatty acid concentrations, which influence intrahepatic triglyceride (IHTG) content and metabolic function. Objective: The objective of the study was to determine the effects of fenofibrate and nicotinic acid therapy on IHTG content and cardiovascular risk factors. Experimental Design and Main Outcome Measures: We conducted a randomized, controlled trial to determine the effects of fenofibrate (8 wk, 200 mg/d), Niaspan (16 wk, 2000 mg/d), or placebo (8 wk) on IHTG content, very low-density lipoprotein (VLDL) kinetics, and insulin sensitivity. Setting and Participants: Twenty-seven obese subjects with nonalcoholic fatty liver disease (body mass index 36 ± 1 kg/m2, IHTG 23 ± 2%) were studied at Washington University. Results: Neither fenofibrate nor Niaspan affected IHTG content, but both decreased plasma TG, VLDL-TG, and VLDL-apolipoprotein B concentrations (P < 0.05). Fenofibrate increased VLDL-TG clearance from plasma (33 to 54 ml/min; P < 0.05) but not VLDL-TG secretion. Niaspan decreased VLDL-TG secretion (27 to 15 μmol/min; P < 0.05) without affecting clearance. Both fenofibrate and Niaspan decreased VLDL-apolipoprotein B secretion (1.6 to 1.2 and 1.3 to 0.9 nmol/min, respectively; P < 0.05). Niaspan reduced hepatic, adipose tissue, and muscle insulin sensitivity (P < 0.05), whereas fenofibrate had no effect on insulin action. Conclusions: Fenofibrate and Niaspan decrease plasma VLDL-TG concentration without altering IHTG content. However, the mechanism responsible for the change in VLDL-TG concentration is different for each drug; fenofibrate increases plasma VLDL-TG clearance, whereas nicotinic acid decreases VLDL-TG secretion.Fenofibrate and niaspan decrease plasma VLDL-triglyceride concentration by altering VLDL-triglyceride kinetics without altering intrahepatic triglyceride content.