Effect of Ezetimibe on Hepatic Fat, Inflammatory Markers, and Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Subjects on a Weight Loss Diet
- Dick C. Chan, PHD,
- Gerald F. Watts, MD, DSC,
- Seng Khee Gan, MD, PHD,
- Esther M.M. Ooi, PHD and
- P. Hugh R. Barrett, PHD
- From the Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
- Corresponding author: Gerald F. Watts, gerald.watts{at}uwa.edu.au.
Abstract
OBJECTIVE Nonalcoholic fatty liver disease is highly prevalent in obese and type 2 diabetic individuals and is strongly associated with dyslipidemia and inflammation. Weight loss and/or pharmacotherapy are commonly used to correct these abnormalities.
RESEARCH DESIGN AND METHODS We performed a 16-week intervention trial of a hypocaloric, low-fat diet plus 10 mg/day ezetimibe (n = 15) versus a hypocaloric, low-fat diet alone (n = 10) on intrahepatic triglyceride (IHTG) content, plasma high sensitivity–C-reactive protein (hs-CRP), adipocytokines, and fetuin-A concentrations and apolipoprotein (apo)B-100 kinetics in obese subjects. ApoB-100 metabolism was assessed using stable isotope tracer kinetics and compartmental modeling; liver and abdominal fat contents were determined by magnetic resonance techniques.
RESULTS Both weight loss and ezetimibe plus weight loss significantly (all P < 0.05) reduced body weight, visceral and subcutaneous adipose tissues, insulin resistance and plasma triglycerides, VLDL–apoB-100, apoC-III, fetuin-A, and retinol-binding protein-4 and increased plasma adiponectin concentrations. Compared with weight loss alone, ezetimibe plus weight loss significantly (all P < 0.05) decreased IHTG content (−18%), plasma hs-CRP (−53%), interleukin-6 (−24%), LDL cholesterol (−18%), campesterol (−59%), and apoB-100 (−14%) levels, with a significant increase in plasma lathosterol concentrations (+43%). The LDL–apoB-100 concentration also significantly fell with ezetimibe plus weight loss (−12%), chiefly owing to an increase in the corresponding fractional catabolic rate (+29%). The VLDL–apoB-100 secretion rate fell with both interventions, with no significant independent effect of ezetimibe.
CONCLUSIONS Addition of ezetimibe to a moderate weight loss diet in obese subjects can significantly improve hepatic steatosis, inflammation, and LDL–apoB-100 metabolism.
Footnotes
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Clinical trial reg. no. ACTRN12606000152527, ANZCTR.org.au.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received September 22, 2009.
- Accepted February 8, 2010.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
- © 2010 by the American Diabetes Association.
