ABC | Volume 113, Nº5, November 2019

Original Article High-Lard and High-Cholesterol Diet, but not High-Lard Diet, Leads to Metabolic Disorders in a Modified Dyslipidemia Model Lidiane B. Muniz, Aline M. Alves-Santos, Fabricio Camargo, Danieli Brolo Martins, Mara Rubia N. Celes , Maria Margareth V. Nave s Universidade Federal de Goiás, Goiania, GO – Brazil Mailing Address: Maria Margareth V. Naves • Universidade Federal de Goiás - Faculdade de Nutrição - Laboratório de Nutrição Experimental – Rua 227, quadra 68, Setor Leste Universitário, Postal Code 74605-080, Goiânia, GO – Brazil E-mail: mmvnaves@gmail.com Manuscript received August 27, 2018, revised manuscript December 03, 2018, accepted January 23, 2019 DOI: 10.5935/abc.20190149 Abstract Background: In view of the increased global prevalence of cardiovascular and hepatic diseases, the diet lipid content and its relationship with the accumulation of fat in hepatocytes have been investigated as key factors in preventing these diseases. Objective: To evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model. Methods: We divided 24 adult male Wistar rats into three groups: standard diet (STD - 4% lipids), high-lard diet (HLD - 21% lard), and high-lard and high-cholesterol diet (HL/HCD - 20% lard, 1% cholesterol, 0.1% cholic acid). After six weeks of treatment, blood and liver were collected for biochemical (serum lipid profile and liver enzymes) and morphological analyses. Statistical analysis included one-way analysis of variance (ANOVA), followed by Tukey test for mean comparisons, and a 5% probability was considered statistically significant. Results: AnimalsfedHL/HCDshowedincreasedtotalcholesterol,triacylglycerol,LDL-c,non-HDL-c,alanineaminotransferase (ALT), and aspartate aminotransferase (AST) serum levels compared to those fed STD. In addition, the HL/HCD animals presented higher relative liver weight, with moderate macrovesicular hepatic steatosis and inflammatory infiltrate. Conclusion: A high-fat diet with lard (20%) and cholesterol (1%) triggered dyslipidemia with severe liver damage in rats in a shorter experimental time than the previously reported models. The high-lard diet without supplementation of cholesterol led to body weight gain, but not to dyslipidemia. (Arq Bras Cardiol. 2019; 113(5):896-902) Keywords: Dietary Fats; Cholesterol; Lipid Metabolism; Fatty Liver; Inflammation; Rats. Introduction The worldwide prevalence of metabolic diseases and associated health complications have increased in recent decades. Excess body fat, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and dyslipidemia lead tometabolic disorders related to higher risks of developing cardiovascular diseases. 1 NAFLD ranges from a minor hepatocyte fat accumulation to more severe stages of inflammatory necrosis, with or without fibrosis. Studies indicate an association betweenNAFLDand insulin resistance, hepatocyte inflammation, and lipid metabolism impairment, 2,3 as most NAFLD patients present dyslipidemia. 4 Dyslipidemia is characterized by increased levels of triacylglycerol (TG) and low-density lipoprotein cholesterol (LDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). 5 Hypercholesterolemia (isolated LDL-c increase) and hypertriglyceridemia (isolated TG increase) are themost common forms of dyslipidemia. 6 In general, lipid metabolism imbalance results from the interaction between genetics and environmental factors, such as eating habits, especially lipid consumption. Therefore, diet lipid content has been investigated as a key factor in preventing cardiovascular and hepatic diseases. 7 Experimental studies with high-fat diets have used very high contents of dietary fat (about 50% of the diet composition), in short-period (four weeks) protocols, without finding serum lipid impairment. 8,9 On the other hand, studies testing lipid concentrations closer to human consumption have been performed during a relatively long experimental time, as in previous reports with rats (21% fat for 9 weeks) 10 and with mice (15% to 20% fat for 12 to 16 weeks). 11,12 In this context, this study aimed to evaluate the metabolic effects of a high-lard diet supplemented or not with cholesterol on a modified dyslipidemia model, with shorter experimentation time and lower diet lipid concentration compared to previous reports. Methods Animals, diets, and experimental design The experiment was carried out with adult male Wistar rats provided by the University of São Paulo (Ribeirão Preto, Brazil). The rats were kept in plastic cages (2 animals/cage) for 896