title: Rats on a high-energy diet showing no weight gain present with ultrastructural changes associated with liver fibrosis.
abstract: Sibutramine is widely used as a weight-loss substance in the treatment of obesity and is a selective inhibitor of the neuronal reuptake of serotonin and noradrenaline. Although banned, it is often a hidden ingredient in herbal and dietary supplements that are widely used by the general public. Various weight loss products, including sibutramine, have successfully been tested in animal models of diet-induced obesity. In the female Sprague-Dawley rat model, fed a high-energy diet that did not produce a significant increase in BMI, the cellular structure of the liver was evaluated using transmission electron microscopy. Compared to controls showing no damage, the livers of rats fed a high-energy diet were found to have increased fibrosis without steatosis, while for rats fed high-energy diet with sibutramine, fibrosis was increased and steatosis had developed. In conclusion, in female rats fed a high-energy diet that does not result in weight gain hepatic fibrosis occurs without steatosis. In these rats the co-administration of sibutramine increases the degree of fibrosis and steatosis develops. Although it has been widely believed that sibutramine is not hepatotoxic, this study clearly shows that at an ultrastructural level, rats fed a high-energy diet treated with sibutramine show signs of hepatotoxicity.
authors.affiliation: Department of Anatomy, Faculty of Health Sciences, University of Pretoria, Arcadia, South Africa. nanette.oberholzer@up.ac.za
authors.forename: Hester Magdalena
authors.initials: HM
authors.lastname: Oberholzer
authors.forename: Megan Jean
authors.initials: MJ
authors.lastname: Bester
authors.forename: Ciska
authors.initials: C
authors.lastname: van der Schoor
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000633:toxicity*; D015992:Body Mass Index; D003503:Cyclobutanes / Q000633:toxicity*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D005260:Female; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure*; D008103:Liver Cirrhosis / Q000209:etiology* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D009765:Obesity / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; C058254:sibutramine