Metabolic benefits of marine n-3 fatty acids demonstrated in nonhuman primates.

Rates of obesity, insulin resistance, and metabolic syndrome are increasing in many countries. Diet is an obvious factor that can contribute to the risk of these metabolic conditions, which, in turn, predispose one to type 2 diabetes and cardiovascular disease, major sources of morbidity, mortality, and health expenditure. The key dietary components involved in increasing metabolic risk are subject to much conjecture, but there is a view that increased intake of fructose as dietary sucrose and from high-fructose syrups is a major culprit (1). Recent work in rhesus monkeys demonstrated that a high-carbohydrate, high-fructose diet induced several features of human metabolic syndrome, including obesity, hypertriglyceridemia, and insulin resistance (2). In this issue of The Journal of Nutrition, an article reports on the effects of marine n–3 (v-3) PUFAs in rhesus monkeys fed a high-carbohydrate, high-fructose diet (3). Marine n–3 PUFAs were shown to prevent the hypertriglyceridemia and insulin resistance induced by the high-carbohydrate, high-fructose diet. The animals were adult males aged 12 to 20 y and weighed an average of 15.6 kg at study entry. They were fed a grain-based primate diet providing 11% of energy as fat (>90% as n–6 FAs), 30% of energy as protein, and 59% of energy as carbohydrate, and additionally received 75 g of fructose daily in a 500-mL beverage. The intention of this dietary strategy was to induce metabolic syndrome, in particular obesity, insulin resistance, and dyslipidemia, as previously demonstrated (2). Half of the animals received a treat that included 4 g of fish oil (FO), whereas the treat given to the remaining animals, the control group, contained 4 g of safflower oil, which is rich in the n–6 essential FA linoleic acid. The treats used, which weighed 44 g, also provided unspecified amounts of fat and carbohydrate. The FO provided ;0.64 g EPA and 0.44 g DHA daily. The feeding period was 6 mo. The intention of supplementing the FO was to prevent the development of metabolic syndrome. Over the 6-mo feeding period, the control group demonstrated increases in body weight (13%), total insulin AUC during a 60-min intravenous-glucose-tolerance test (89%), and concentrations of fasting plasma TGs (64%), apoC3 (25%), apoE (29%), fasting insulin (104%), and leptin (30%), and a decrease in concentrations of adiponectin (221%). Thus, the dietary strategy achieved the aims of inducing insulin resistance and dyslipidemia, especially hypertriglyceridemia. Data on body composition are not presented, but the increase in leptin concentration might suggest increased fat mass in the control group. What, then, was the effect of supplementation with FO? The animals that received marine n–3 PUFAs showed an average 9% increase in body weight, less than in the control group, although the increase in body weight was not significantly different between the 2 groups of animals. However, this lack of significant difference between weight gains of 13% and 9% may be due to the small number of animals in each group (9 in the control group and 10 in the FO group) rather than a lack of effect. Also, the difference in weight gain may have becomemore pronounced with a longer duration of feeding. In the FO-supplemented animals, plasma TGs declined by 8.5%, and this change (i.e., the effect of treatment) was different from that in the control group. Likewise, apoC3 decreased in the FO group, and the change from study entry was different from that seen in the control group, whereas the increase in apoE in the FO group was less than that in the control group. Thus, including marine n–3 PUFAs in a high-carbohydrate, high-fructose diet prevented the hypertriglyceridemic effect of that diet. Plasma insulin concentration and the total insulin AUC during a 60-min intravenous-glucose-tolerance test were not significantly altered in the FO group, indicating that FO prevented the diet-induced decline in insulin sensitivity seen in the control group. Plasma leptin was not significantly increased from study entry in the FO group, although there was a small elevation of ;6.5%. Comparison of data for change in leptin concentration from study entry showed that this was significantly less in the FO group than that in the control group, suggesting that FO reduces the development of adiposity induced by the high-carbohydrate, high-fructose diet. Curiously, FO did not affect the diet-induced decrease in plasma adiponectin. This study provides sound evidence to support that marine n–3 PUFAs have effects that can prevent the deleterious metabolic consequences of a diet high in carbohydrates, including a substantial amount of fructose. That these effects were observed in nonhuman primates is a significant advance, because much of the existing data of this type come from studies in rodents and rabbits; many of these small animals have significant differences in diet, metabolic rate, and lipid metabolism compared with humans, limiting the ability to translate the findings. Nevertheless, the diet of the rhesus monkeys studied here was rather different from a typical human diet. Dietary protein was higher than in most human diets, whereas fat, at 11% of energy, was lower than in most Western diets. It would be interesting to study the effect of n–3 FAs in this sort of high-carbohydrate, 1 Author disclosures: P. C. Calder serves on the Danone Scientific Advisory Board on Immunity and Allergy, on the Clinical Advisory Board of Pronova BioPharma, and on the scientific advisory boards of Aker Biomarine and of Smartfish; he acts as a consultant to the Danone Research Centre for Specialised Nutrition, Vifor Pharma, Pfizer, Enzymotec, and Amarin Corporation, and has received speaking honoraria from Fresenius Kabi, B. Braun, Abbott Nutrition, Baxter Healthcare, Nestlé, Unilever, and DSM. * To whom correspondence should be addressed. E-mail: pcc@soton.ac. uk.