Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

Lipids in Health and Disease Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats Uberdan Guilherme Mendes de Castro 0 3 Robson Augusto Souza dos Santos 2 Marcelo Eustquio Silva 0 3 Wanderson Geraldo de Lima 0 1 3 4 Maria Jos Campagnole-Santos 2 Andria Carvalho Alzamora 0 1 3 4 5 0 Nucleo de Pesquisa em Ciencias Biologicas, Universidade Federal de Ouro Preto , Ouro Preto, MG , Brazil 1 Departamento de Ciencias Biologicas, Instituto de Ciencias Exatas e Biologicas, Universidade Federal de Ouro Preto , Morro do Cruzeiro, Ouro Preto, MG 35 400-000 , Brazil 2 Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais , Belo Horizonte, MG , Brazil 3 Nucleo de Pesquisa em Ciencias Biologicas, Universidade Federal de Ouro Preto , Ouro Preto, MG , Brazil 4 Departamento de Ciencias Biologicas, Instituto de Ciencias Exatas e Biologicas, Universidade Federal de Ouro Preto , Morro do Cruzeiro, Ouro Preto, MG 35 400-000 , Brazil 5 Departamento de Ciencias Biologicas, Nucleo de Pesquisa em Ciencias Biologicas, Universidade Federal de Ouro Preto , Ouro Preto, MG , Brazil Background: The metabolic syndrome (MS) is characterized by variable coexistence of metabolic and pathophysiological alterations which are important risk factors for developing of type II diabetes and/or cardiovascular diseases. Increased of MS patients in worldwide has stimulated the development of experimental models. However, it is still challenging to find an dietetic model that most closely approximates human MS and, in addition, is not yet fully established the effect of different diets of MS in lipid metabolism in rats of different ages. The aim of this study was to evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition and define the most appropriate diet for inducing the characteristic disturbances of the human MS in rats of different ages. Methods: Young (4 weeks old) and adult rats (12 weeks old) were given a high-fat (FAT) or high-fructose diet (FRU) for 13 weeks and biochemical, physiological, histological and biometric parameters were evaluated. Results: In young rats, the FAT diet induced increased mean blood pressure (MAP) and heart rate (HR), body weight after 6 to 10 weeks, and in the 13th week, increased the liver, mesenteric, retroperitoneal and epididymal fat weights, fasting glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and reduced HDL cholesterol; and also induced non-alcoholic fatty liver disease (NAFLD) and renal inflammatory infiltrates. In adult rats, the FRU diet induced transient elevations of MAP and HR in the 6th week, and, at 13 weeks, increased fasting glucose, triglycerides, total cholesterol, AST and ALT; increased liver, kidneys and retroperitoneal fat weights; and induced macrovesicular and microvesicular NAFLD, the presence of fat cells in the kidney, glomerular sclerosis, and liver and kidney inflammation. Additionally, the FAT and FRU diets induced, respectively, increases in liver glycogen in adults and young rats. Conclusions: Our data show that FRU diet in adult rats causes biggest change on metabolism of serum lipids and lipid accumulation in liver and kidney, while the FAT diet in young rats induces elevation of MAP and HR and higher increased visceral lipid stores, constituting the best nutritional interventions to induce MS in rats. High-fat diet; High-fructose diet; Metabolic syndrome; Rats of different ages; NAFLD - Background Metabolic syndrome (MS) is a pathological condition in which three or more of the following risk factors are present: central obesity, high plasma triglyceride levels, low plasma HDL levels, high cholesterol, hyperglycemia, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), endothelial dysfunction, insulin resistance (IR), and/or hypertension [1,2]. These metabolic abnormalities observed during MS are important risk factors for developing cardiovascular disease [3,4] and are associated with the development of type II diabetes [5,6]. The development and establishment of MS are mainly related to the consumption of high-fat diets and/or highcarbohydrate diets [7]. Epidemiological studies have shown that consumption of high-fat diets ( 30% of energy from fat) is correlated with high rates of overweight, central obesity and MS [8,9]. Increasing evidence also associates the consumption of a diet high in carbohydrates, such as fructose, with high prevalences of obesity, IR, hypertension and MS [10]. Therefore, the increasing consumption of fructose-rich beverages and/or foods sweetened with table sugar, corn syrup and other preparations and/or processed products containing fructose is of great concern [11]. The increased number of MS patients worldwide has stimulated the development of experimental models that mimic the characteristics of human MS [12], in attempts to understand the biochemical, physiological and pathological alterations involved in the development and maintenance of excess body fat and MS [7]. Several genetic models mimic many of the features of MS occurring in humans, such as obese Zucker rats, obese spontaneously hypertensive rats (Koletsky rats) and Strokeprone SHR-fatty (fa/fa) rats [13]. However, animal models that develop characteristics of MS without genetic manipulation, but only through consumption of specific nutritionally unbalanced diets are increasingly important [14] for use in simulating the most common cause of human MS. Despite the large volume of published studies using experimental models of MS, it is still challenging to find a model that most closely approximates human MS. Experimental models of diet-induced MS vary widely in the induction of MS disturbances [15-18], mainly due to the wide variation in the proportion and/or the types of nutrients that compose the diets and/or the different ages of the animals used. This wide variability of the protocols used in studies on MS limits the reproducibility of the dietary treatments used and comparisons of published data, making clear the need for a precise definition of the nutritional intervention to induce in animal models, the disturbances typical of human MS. In addition, is not yet fully established the effect of different diets of MS in lipid metabolism and ectopic fat deposition in rats of different ages. This study submitted rats of different ages (young and old) to the two main diets used in the literature to induce MS, the high-fat diet [7,19] and high-fructose diet [20,21], and evaluated different biometric, physiological, biochemical and histological parameters in order to define the most appropriate dietary treatment to induce the characteristic disturbances of human MS, and evaluate the effect of different diets of MS in lipid metabolism and ectopic fat deposition in rats of different ages. Methods Animals The study used male Fischer rats, newly (...truncated)