Hepatic effects of rosiglitazone in rats with the metabolic syndrome.
Rats given fructose-enriched diet develop many characteristics of the human metabolic syndrome and non-alcoholic fatty liver disease. In this study, we characterized the hepatic effects of rosiglitazone in fructose-enriched diet rats. Rats were randomly divided into three groups. One group was maintained on standard rat chow diet for 6 weeks, whereas the other two groups were given fructose-enriched diet for 6 weeks. Four weeks after the initiation of fructose-enriched diet, one of the fructose-enriched diet groups was also given rosiglitazone (10 mg/kg/day) for an additional 2 weeks. Rosiglitazone administration to the fructose-enriched diet rats was associated with decreases in the following parameters: blood pressure (-17%), plasma triglycerides (-62%), hepatic total lipids (-19%), hepatic triglycerides (-61%), hepatic malondialdehyde (-88%), glutathione reductase activity (-84%). An increase in adiponectin plasma levels (+329%), hepatic phospholipids (+46%), hepatic alpha-tocopherol concentrations (+24%) and hepatic paraoxonase activity (+68%) was observed. Rosiglitazone caused a decrease in hepatic macrovesicular steatosis score but no change in hepatic fibrosis. Administration of rosiglitazone, to rats with the metabolic syndrome has limited hepatic favourable effects: it improves hepatic lipid metabolism, decreases macrovesicular steatosis and improves some of the hepatic oxidative-anti-oxidative milieu but has no effect on hepatic fibrosis.
Ackerman
Zvi
Z
Department of Medicine, Mount Scopus Campus, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. zackerman@hadassah.org.il
Oron-Herman
Mor
M
Pappo
Orit
O
Peleg
Edna
E
Safadi
Rifaat
R
Schmilovitz-Weiss
Hemda
H
Grozovski
Maria
M
D052242:Adiponectin / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D005632:Fructose / Q000008:administration & dosage; D005980:Glutathione Reductase / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000188:drug therapy*; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000378:metabolism
D052242:Adiponectin; D007004:Hypoglycemic Agents; D008055:Lipids; D010743:Phospholipids; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005632:Fructose; D008315:Malondialdehyde; D005980:Glutathione Reductase; D043303:Aryldialkylphosphatase; D024502:alpha-Tocopherol