Fructose-induced fatty liver disease: hepatic effects of blood pressure and plasma triglyceride reduction.
The most known risk factor for nonalcoholic fatty liver disease (NAFLD) is the metabolic syndrome. In this study, we characterized changes in liver pathology, hepatic lipid composition, and hepatic iron concentration (HIC) occurring in rats given fructose-enriched diet (FED), with and without therapeutic maneuvers to reduce blood pressure and plasma triglycerides. Rats were given FED or standard rat chow for 5 weeks. Rats on FED were divided into 4 groups: receiving amlodipine (15 mg/kg per day), captopril (90 mg/kg per day), bezafibrate (10 mg/kg per day) in the last 2 weeks, or a control group that received FED only. FED rats had hepatic macrovesicular and microvesicular fat deposits develop, with increase in hepatic triglycerides (+198%) and hepatic cholesterol (+89%), but a decrease in hepatic phospholipids (-36%), hypertriglyceridemia (+223%), and hypertension (+15%), without increase in HIC. Amlodipine reduced blood pressure (-18%), plasma triglycerides (-12%), but there was no change in hepatic triglycerides and phospholipids concentrations. Captopril reduced blood pressure (-24%), plasma triglycerides (-36%), hepatic triglycerides (-51%), and hepatic macrovesicular fat (-51%), but increased HIC (+23%), with a borderline increase in hepatic fibrosis. Bezafibrate reduced plasma triglycerides (-49%), hepatic triglycerides (-78%), hepatic macrovesicular fat (-90%), and blood pressure (-11%). We conclude that FED rats can be a suitable model for human NAFLD. Drugs administered to treat various aspects of the metabolic syndrome could have hepatic effects. An increase in HIC in rats with NAFLD could be associated with increased hepatic fibrosis.
Ackerman
Zvi
Z
Hebrew University Hadassah Medical Center, Jerusalem, Israel. zackerman@hadassah.org.il
Oron-Herman
Mor
M
Grozovski
Maria
M
Rosenthal
Talma
T
Pappo
Orit
O
Link
Gabriela
G
Sela
Ben-Ami
BA
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001629:Bezafibrate / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004032:Diet; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D005632:Fructose / Q000008:administration & dosage*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000037:antagonists & inhibitors / Q000097:blood* / Q000378:metabolism
D000959:Antihypertensive Agents; D000960:Hypolipidemic Agents; D014280:Triglycerides; D017311:Amlodipine; D005632:Fructose; D002216:Captopril; D007501:Iron; D001629:Bezafibrate