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Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet.

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.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Chan DC,Watts GF,Gan SK,Ooi EM,Barrett PH

doi

10.2337/dc09-1765

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

1134-9

issue

eissn

0149-5992

issn

1935-5548

pii

dc09-1765

journal_volume

pub_type

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Effect of ezetimibe on hepatic fat, inflammatory markers, and apolipoprotein B-100 kinetics in insulin-resistant obese subjects on a weight loss diet.