title: Several statins increase body and liver fat accumulation in a model of metabolic syndrome.
abstract: Statins are a family of drugs used in hypercholesterolemia. The aim of this study was to analyze the effect of statins on body and liver fat accumulation in obese Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats from six statin groups were treated with pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg body weight/day. After 6 weeks, liver and white adipose tissue from intra-abdominal and subcutaneous locations were dissected and weighed. Subcutaneous adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin treated rats was significantly increased. Fatty acid synthase (FAS) activity was increased by the administration of fluvastatin and lovastatin, as was glucose-6-P dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No changes were observed in malic enzyme (ME) activity. Furthermore, heparin-releasable lipoprotein lipase (HR-LPL) was increased in all groups where the subcutaneous depot was increased, and total LPL increased only in rosuvastatin and fluvastatin-treated groups. With regard to liver, there were no changes in weight but the amount of triacylglycerols was increased in rosuvastatin group, as well as its liver damage was higher. In this group FAS and G6PDH activities were increased and no changes were observed in ME, acyl CoA oxidase (ACO) and carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the exception of simvastatin, worsen insulin resistance. These results show that statins have different effects on body fat accumulation. Moreover, rosuvastatin also shows a prosteatotic effect. These results should be taken into account for statin choice in prescription.
authors: Nutrition and Obesity Group, Department of Nutrition and Food Sciences, University of Pais Vasco (UPV/EHU), Vitoria, Spain. leixuri.aguirre@ehu.es
authors: L
authors: L
authors: Aguirre
authors: E
authors: E
authors: Hijona
authors: M T
authors: MT
authors: Macarulla
authors: A
authors: A
authors: Gracia
authors: I
authors: I
authors: Larrechi
authors: L
authors: L
authors: Bujanda
authors: L
authors: L
authors: Hijona
authors: M P
authors: MP
authors: Portillo
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D004195:Disease Models, Animal; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050155:Lipogenesis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; D005954:Glucosephosphate Dehydrogenase; D054890:Fatty Acid Synthase, Type I; D008071:Lipoprotein Lipase