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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Elisa Fabbrini
  • B Selma Mohammed
  • Kevin M Korenblat
  • Magkos, Faidon
  • Jennifer McCrea
  • Bruce W Patterson
  • Samuel Klein

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. 

Expermiental 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/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.

OriginalsprogEngelsk
TidsskriftJournal of Clinical Endocrinology and Metabolism
Vol/bind95
Udgave nummer6
Sider (fra-til)2727-2735
Antal sider9
ISSN0021-972X
DOI
StatusUdgivet - 2010
Eksternt udgivetJa

Bibliografisk note

(Ekstern)

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