Format

Send to

Choose Destination
Diabetes Care. 2010 May;33(5):1134-9. doi: 10.2337/dc09-1765. Epub 2010 Feb 25.

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

Author information

1
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.

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.

PMID:
20185740
PMCID:
PMC2858190
DOI:
10.2337/dc09-1765
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center