Published Online
on April 11, 2005

A more recent version of this article appeared on May 1, 2005

This Article Full Text (PDF) Data Supplement All Versions of this Article: 45/5/1012    most recent 01.HYP.0000164570.20420.67v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ackerman, Z. Articles by Sela, B.-A. Search for Related Content PubMed PubMed Citation Articles by Ackerman, Z. Articles by Sela, B.-A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMLODIPINE BESYLATE CAPTOPRIL FRUCTOSE IRON Related Collections Lipids Animal models of human disease Other hypertension Glucose intolerance

Submitted on November 16, 2004
Revised on December 8, 2004

Fructose-Induced Fatty Liver Disease. Hepatic Effects of Blood Pressure and Plasma Triglyceride Reduction

Zvi Ackerman^*; Mor Oron-Herman; Maria Grozovski; Talma Rosenthal; Orit Pappo; Gabriela Link; and Ben-Ami Sela

From the Hebrew University Hadassah Medical Center (Z.A., O.P.), Jerusalem; Tel Aviv University Sackler Faculty of Medicine (M.O-H., T.R., B.-A.S.), Institute of Chemical Pathology Sheba Medical Center (M.O.-H., B.-A.S.), Tel Hashomer; Department of Human Nutrition and Metabolism (G.L.), Hebrew University Medical School (Z.A., O.P., G.L.), Jerusalem; Ort Braude College of Engineering (M.G.), Karmiel, Israel.

^* To whom correspondence should be addressed. E-mail: zackerman{at}hadassah.org.il.

Abstract--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.

Key words: amlodipine • bezafibrate • captopril • iron • nonalcoholic steatohepatitis

This article has been cited by other articles:

				T. Kawasaki, K. Igarashi, T. Koeda, K. Sugimoto, K. Nakagawa, S. Hayashi, R. Yamaji, H. Inui, T. Fukusato, and T. Yamanouchi Rats Fed Fructose-Enriched Diets Have Characteristics of Nonalcoholic Hepatic Steatosis J. Nutr., November 1, 2009; 139(11): 2067 - 2071. [Abstract] [Full Text] [PDF]

				R. J. Johnson, S. E. Perez-Pozo, Y. Y. Sautin, J. Manitius, L. G. Sanchez-Lozada, D. I. Feig, M. Shafiu, M. Segal, R. J. Glassock, M. Shimada, et al. Hypothesis: Could Excessive Fructose Intake and Uric Acid Cause Type 2 Diabetes? Endocr. Rev., February 1, 2009; 30(1): 96 - 116. [Abstract] [Full Text] [PDF]

				S. Thuy, R. Ladurner, V. Volynets, S. Wagner, S. Strahl, A. Konigsrainer, K.-P. Maier, S. C. Bischoff, and I. Bergheim Nonalcoholic Fatty Liver Disease in Humans Is Associated with Increased Plasma Endotoxin and Plasminogen Activator Inhibitor 1 Concentrations and with Fructose Intake J. Nutr., August 1, 2008; 138(8): 1452 - 1455. [Abstract] [Full Text] [PDF]

				I. Aeberli, M. B Zimmermann, L. Molinari, R. Lehmann, D. l'Allemand, G. A Spinas, and K. Berneis Fructose intake is a predictor of LDL particle size in overweight schoolchildren Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1174 - 1178. [Abstract] [Full Text] [PDF]