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.
BACKGROUND
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.


METHODS
Twenty-seven obese subjects with nonalcoholic fatty liver disease (body mass index 36 +/- 1 kg/m(2), 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 micromol/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.
Fabbrini
Elisa
E
Center for Human Nutrition, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Mohammed
B Selma
BS
Korenblat
Kevin M
KM
Magkos
Faidon
F
McCrea
Jennifer
J
Patterson
Bruce W
BW
Klein
Samuel
S
D000328:Adult; D001055:Apolipoproteins B / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D004311:Double-Blind Method; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D009525:Niacin; D011345:Fenofibrate