Research ArticleEffects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats
Introduction
The role of selected dietary fatty acids in the prevention or progression of chronic diseases has generated long-standing interest [1], [2], [3], [4], [5]. It is now generally accepted that the type of dietary fat plays a far more significant role in health and disease than the absolute amount [6], [7], [8]. Depending on the nutritional lifestyle, dietary fat includes varying quantities of saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA), mainly as n-3 and n-6 PUFA [6]. The Western diet, characterized by excessive amounts of SFA, n-6 PUFA and trans fatty acids with decreased intake of n–3 PUFA, has been implicated in chronic diseases such as obesity, diabetes, cardiovascular and renal diseases as well as inflammatory diseases such as arthritis [6], [7], [8], [9]. We have reported that the chronic changes following a high-carbohydrate, high-fat diet in rats mimic the metabolic syndrome in humans [10] and, further, that interventions with natural products such as purple carrots [11], olive leaf extract [12], chia seeds [13] and rutin [14] can reverse these changes.
The three major dietary n-3 PUFA, α-linolenic acid (ALA; C18:3n-3), eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) may produce distinctly different responses on the risk factors for metabolic syndrome [15]. Although n-3 PUFA are a well-studied class of bioactive molecules, the effectiveness of ALA, the primary fatty acid of the n-3 pathway, in metabolic syndrome is less clear than its elongated metabolites, EPA and DHA. Further, it is still unclear if EPA and DHA have independent physiological effects as most studies have only studied EPA and DHA mixtures such as fish oil capsules or oily fish diet or supplements [15] rather than the individual fatty acids. Also, the paucity of comparative studies involving all three individual n-3 PUFA provides a weak basis for assuming different responses in the pathophysiology of chronic diseases [15].
In high-carbohydrate, high-fat-diet fed rats, we have shown that chia seed, one of the richest dietary sources of ALA, improved insulin sensitivity and glucose tolerance, reduced visceral adiposity, decreased hepatic steatosis and reduced cardiac and hepatic inflammation and fibrosis without changes in plasma lipids or blood pressure [13]. Chia seed supplementation induced lipid redistribution with lipid trafficking away from the visceral fat and liver with increased accumulation in the heart. These effects were associated with the depletion of MUFA, the products of stearoyl-CoA desaturase-1 (SCD-1) activity, in the heart, liver and adipose tissue together with an increase in SFA concentrations. The C18:1trans-7 was preferentially stored in the adipose tissue; the relatively inert C18:1n-9 was stored in sensitive organs such as the liver and the heart, and C18:2n-6, the parent fatty acid of the n-6 pathway, was preferentially metabolized. Based on these results, we suggested that these effects were mediated by ALA rather than by metabolism to EPA or DHA [13].
In this study, we compared the effects of ALA-rich chia oil and fish oils enriched with either EPA or DHA on cardiovascular, hepatic and metabolic parameters in a diet-induced rat model of the human metabolic syndrome. Additionally, we investigated the changes in fatty acid composition of plasma, adipose tissue, liver, heart and skeletal muscle after dietary supplementation with these n-3 PUFA. In addition to serving as a control to the high-carbohydrate, high-fat diet (24% fat, mostly trans and SFA without n-3 PUFA), a corn starch-rich diet (0.8% fat, with comparable proportions of SFA, MUFA and PUFA without trans and little n-3 PUFA) also served as a model of a low fat diet to ascertain the responses to the individual n-3 PUFA without interactions with other dietary fatty acids (Table 1).
Section snippets
Rats and diets
The experimental groups consisted of 96 male Wistar rats (9–10 weeks old) supplied by The University of Queensland Biological Resources unit and individually housed in a temperature-controlled, 12-h light/dark cycle environment with ad libitum access to water and the group-specific rat diet at the University of Southern Queensland Animal House. All experimentation was approved by the Animal Experimentation Ethics Committees of The University of Queensland and the University of Southern
Dietary intake, body composition and plasma biochemistry
Food and water intake was decreased in H, HA, HE and HD rats compared to C, CA, CE and CD rats, respectively (Table 2). With the exception of CE rats, n-3 oil supplementation did not alter food or water intakes in any of the groups (Table 2). ALA-rich chia oil, EPA oil and DHA oil supplementation increased energy intakes compared to C and H rats (Table 2). Feed conversion efficiency was decreased in CA, CE, CD and HD rats compared to their respective controls (Table 2). All oil-supplemented
Discussion
Epidemiological, human and animal studies suggest that increased dietary n-3 PUFA (ALA, EPA and DHA) may decrease the risk factors for metabolic syndrome including hyperglycemia, insulin resistance, hypertension, dyslipidemia and central adiposity [15]. However, these n-3 PUFA have not been previously compared individually in the same study to differentiate the physiological responses elicited by each fatty acid in models of metabolic syndrome. Moreover, ALA is the least studied of n-3 PUFA
Acknowledgments
We thank Mr. Greg Jardine, Dr Red Nutraceuticals, Mt. Nebo, Qld, Australia, for the supply of chia oil, EPA oil and DHA oil. We thank Mr Jason Brightwell, The Prince Charles Hospital, Brisbane, Australia for the acquisition of echocardiographic images. We thank Dr Kate Kauter, Department of Biological and Physical Sciences, University of Southern Queensland and Dr Jennifer Waanders, School of Agriculture and Food Sciences, The University of Queensland for their assistance and expert advice in
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