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.

• Authors: Dick C Chan, Gerald F Watts, Seng Khee Gan, Esther M M Ooi, P Hugh R Barrett
• Journal: Diabetes care (Diabetes Care) Vol. 33 Issue 5 Pg. 1134-9 (May 2010) ISSN: 1935-5548 [Electronic] United States
• PMID: 20185740 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• AHSG protein, human
• Adipokines
• Anticholesteremic Agents
• Apolipoprotein B-100
• Azetidines
• Biomarkers
• Blood Proteins
• Triglycerides
• alpha-2-HS-Glycoprotein
• C-Reactive Protein
• Ezetimibe

Topics

• Adipokines (blood)
• Aged
• Anticholesteremic Agents (therapeutic use)
• Apolipoprotein B-100 (blood)
• Azetidines (therapeutic use)
• Biomarkers (blood)
• Blood Proteins (metabolism)
• Body Composition
• C-Reactive Protein (metabolism)
• Combined Modality Therapy
• Diet, Reducing
• Ezetimibe
• Fatty Liver (drug therapy, immunology, metabolism)
• Humans
• Insulin Resistance
• Liver (metabolism)
• Middle Aged
• Obesity (drug therapy, immunology, metabolism)
• Patient Compliance
• Triglycerides (metabolism)
• Weight Loss
• alpha-2-HS-Glycoprotein