Original Research Hepatomegaly Induced by Trans-10,cis-12 Conjugated Linoleic Acid in Adult Hamsters Fed an Atherogenic Diet Is Not Associated with Steatosis Jonatan Miranda, DS, Alfredo Ferna ´ndez-Quintela, PhD, Itziar Churruca, PhD, Vı ´ctor M. Rodrı ´guez, PhD, Edurne Simo ´n, PhD, and Marı ´a P. Portillo, PhD Department of Nutrition and Food Science, University of Paı ´s Vasco, Paseo de la Universidad 7, 01006 Vitoria, SPAIN Key words: conjugated linoleic acid, fatty acid oxidation, lipogenesis, liver, steatosis Objective: To study the effects of trans-10,cis-12 conjugated linoleic acid (CLA) on liver size and composition, as well as on hepatic lipogenesis and fatty acid oxidation, in adult hamsters. Methods: Sixteen male Syrian Golden hamsters (8-month-old; initial body weight 167  5 g) were divided into two groups and fed on atherogenic diets supplemented either with 0.5% linoleic acid or trans-10,cis-12 CLA, for 6 weeks. Liver lipids, fatty acid profile, protein, water and DNA contents were analysed. The activity and expression of several enzymes involved in liver fatty oxidation and lipogenesis were assessed, as was the expression of transcriptional factors controlling these enzymes. Results: The addition of CLA to the diet led to significantly greater liver weight due to hyperplasia. No changes were observed in liver composition. CLA did not modify the expression or the activity of analysed oxidative enzymes. With regard to lipogenic enzymes, an increase in the expression and the activity of acetyl-CoA carboxylase was found. Conclusions: These results show that the expected body fat-lowering effect of trans-10,cis-12 CLA, observed in young rodents, is not found in adult hamsters. The lack of increase in liver fatty acid oxidation, help to explain why that effect was not found in these animals. Further, the CLA treatment-induced hepatomegaly is a consequence of hyperplasia. INTRODUCTION The reduction in body fat accumulation induced by trans- 10,cis-12 conjugated linoleic acid CLA has been widely dem- onstrated in animal models [1]. This effect is not exclusively due to the modifications induced by this CLA isomer in adipose tissue metabolism but also to changes produced in liver and skeletal muscle lipid metabolism, such as increased fatty acid oxidation [2– 4]. Thus, the liver is a target organ for the study of the impact of CLA and especially of the trans-10,cis-12 CLA isomer on health. Many studies performed on mice have reported a very strong decrease in body fat, as well as an increase in liver weight associated with severe steatosis, in- duced by CLA [5–10]. However, not all species are similarly CLA-sensitive with regard to the effects on the liver. Thus, we have previously reported that feeding young hamsters trans- 10,cis-12 CLA induced an increase in liver weight associated with an increase in the number of hepatocytes, but not with steatosis. In fact, the animals fed this CLA isomer showed a reduced triacylglycerol content when compared to the controls. This change in lipid amount was due to increased mitochon- drial and peroxisomal fatty acid oxidation [11]. Other authors have also found increased liver size unrelated to fat accumu- lation in hamsters [12]. Address correspondence to: Dr. Marı ´a P. Portillo, Dpt. Nutrition and Food Science, Facultad de Farmacia, Paseo de la Universidad, 7, 01006 Vitoria, SPAIN. E-mail: mariapuy.portillo@ehu.es Conflict of interest: None of the authors had any conflict of interest. Abbreviations: CLA = conjugated linoleic acid, PPAR = peroxisome proliferator-activated receptor, SREBP = sterol regulatory element binding protein, ACC = acetyl-CoA carboxylase, FAS = fatty acid synthase, G6PDH = glucose-6-phosphate dehydrogenase, ME = malic enzyme, CPT-Ia = carnitine palmitoyltransferase-Ia, ACO = acyl-coenzyme A oxidase I. Journal of the American College of Nutrition, Vol. 28, No. 1, 43–49 (2009) Published by the American College of Nutrition 43