Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain
Introduction
For a number of years, n-3 polyunsaturated fatty acids (PUFAs) have been recognized as protective factors of atherosclerosis and subsequent cardiovascular diseases (CVD) [1], [2], [3]. The first evidence relies on epidemiological studies of human populations characterized by their high intake of n-3 long-chain (LC) PUFAs of marine origin [4], [5]. Beneficial reported effects of n-3 LC-PUFAs include reduced plasma lipids [6], [7], [8], thrombogenesis [9] and possibly blood pressure [8].
Besides direct dietary intake, n-3 LC-PUFAs can also derive from the desaturation and elongation of the precursor fatty acid of plant origin, α-linolenic acid (ALA, 18:3n-3). Recent epidemiological data demonstrate inverse associations between dietary ALA and risk of CVD [10], [11], [12], [13]. In the human, ALA and its LC derivatives exhibited similar positive effects on hemostatic factors and thrombogenesis [1] and on blood pressure [14]. The impact of dietary intake of ALA on plasma lipids and lipoproteins is more controversial : no effects [1] or decrease in total cholesterol (TC) and LDL-cholesterol (LDL-C) [15], [16], [17]. In all human studies, and contrary to its LC derivatives, an ALA-rich diet failed to decrease plasma triglycerides (TG) [1], [18], [19]. Much less is known concerning its metabolic targets and mechanisms of action (direct or through its transformation into LC derivatives).
In addition to nutritional agents, hormonal status has an effect on the etiology of CVD. In the human, susceptibility to coronary heart disease is higher in men than in age-matched women. After menopause, the incidence of CVD in women tend to reach that of men, together with an increase in TC, LDL-C, TG and apoB, and a decrease in HDL-cholesterol (HDL-C) [20], [21], [22]. The underlying mechanisms are related to the known effects of estrogens on lipid metabolism, such as a decrease in HDL catabolism via a decrease in hepatic lipase activity and an increase in LDL catabolism via an increase in the number of LDL receptors [23].
In consequence, hormonal influences on lipid metabolism may interact with the impact of nutritional factors and influence the responsiveness to dietary treatment of males and females. Among animal models suitable for investigating the interactions between gender and dietary PUFAs in the susceptibility to CVD, the golden Syrian hamster (Mesocricetus auratus) is probably one of the most relevant. Indeed, among rodents, its lipid metabolism is the less different from that of humans, especially as concerns hepatic cholesterol synthesis [24], [25], plasma lipoprotein profile [26], [27], and bile acid metabolism [28]. Moreover, the hamster is a recognized model for atherosclerosis research, because some strains develop vascular lesions together with hyperlipidemia in response to a diet rich in cholesterol and saturated FA [29], [30], [31]. This effect is more pronounced in males than in females, which supports the hypothesis of the modulation of the response of lipid metabolism to dietary FA by hormonal status [32], [33]. In the hamster, cholesterol metabolism is sensitive to dietary LC-PUFAs however, to our knowledge, the effects of dietary ALA on lipid metabolism has not been investigated in this species.
The present study was therefore designed to determine, in the hamster: 1/ The potential beneficial effects of dietary ALA on lipid metabolism, 2/ The gender-related differences in this metabolism, and 3/ The possible interactions between dietary FA and gender.
Section snippets
Animals and diets
Golden Syrian hamsters (Mesocricetus auratus) were males and females born in our breeding unit (LPN strain). After weaning at 3 weeks of age, 18 hamsters of each gender were bred in colony cages in a temperature- (22°C) and light- (14 hrs day/10 hrs night) controlled room. Males and females were separated, and sterile food pellets and distilled water were provided ad libitum. This commercial diet (UAR113, Villemoisson, France) contained 72.0% cereals, 17.8% soy meal, 6.0% fish meal, 4.2%
Plasma parameters
Hamsters fed the “butter” diet exhibited higher glycaemia and insulinemia, and a higher insulin resistance index calculated by HOMA than hamsters fed the “linseed” diet (Table 2). By contrast, there were no gender-related differences in fasting glycaemia and insulinemia. Plasma concentrations of all lipids (except TG) were significantly lower in animals fed the “linseed” diet, and identical in males and females. Plasma TG concentration was twice higher in males fed the “butter” diet than in the
Effects of an ALA-rich diet on lipid metabolism
In the present study, the “butter” diet was formulated to present some of the nutritional features of diets in western populations, such as a high caloric content, 32% of total energy brought by lipids and a predominance of saturated fatty acids over PUFAs (Table 1). When compared to those fed this western-type diet, male and female hamsters fed the ALA-rich diet for 9 weeks exhibited lower glycaemia, insulinemia and insulin resistance index (Table 2). Similar effects of an ALA rich diet on
Acknowledgements
We would like to thank Mr. Vandeputte and Mr. Beaudoin (the Vandeputte oil factory, Mouscron, Belgium) for the providing of linseed oil. We gratefully acknowledge the skilful help of Nathalie Samson and Sandra Van der Geenst in animal care, the technical assistance of Claudine Verneau and Marc Moqué, and the contribution of Fabien Claveau, who was master student in the laboratory.
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