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


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.
Chan
Dick C
DC
Metabolic Research Centre, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Watts
Gerald F
GF
Gan
Seng Khee
SK
Ooi
Esther M M
EM
Barrett
P Hugh R
PH
D054392:Adipokines / Q000097:blood; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100 / Q000097:blood*; D001384:Azetidines / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D001823:Body Composition; D002097:C-Reactive Protein / Q000378:metabolism; D003131:Combined Modality Therapy; D004038:Diet, Reducing; D000069438:Ezetimibe; D005234:Fatty Liver / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D010349:Patient Compliance; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D054392:Adipokines; D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D001384:Azetidines; D015415:Biomarkers; D001798:Blood Proteins; D014280:Triglycerides; D060749:alpha-2-HS-Glycoprotein; D002097:C-Reactive Protein; D000069438:Ezetimibe