BIOACTIVE FATTY ACID SUPPLEMENTATION AND RISK FACTORS FOR THE METABOLIC SYNDROME

Abstract

Diet plays an important role in the development of chronic metabolic diseases (diabetes, obesity, cardiovascular disease) and as dietary fat consumption has increased, so has the incidence of these disorders. Metabolic syndrome, a clustering of risk factors that includes central obesity, increased plasma triacylglycerol (TG), elevated fasting glucose and glucose intolerance is perhaps the most notorious and aggressive. Animal and human studies indicate that bioactive fatty acids can influence cellular energy metabolism. Using susceptible rodent models (apoE-/- and LDLr-/- mice and Syrian Golden hamsters) this project investigated whether supplementation of a western type diet (WD) with bioactive fatty acids could improve hepatic lipid metabolism, plasma lipoprotein profiles or liver markers of lipogenesis. In mice, dietary supplementation with t-10, c-12 conjugated linoleic acid (CLA) decreased the weight gain induced by high fat diet compared with WD (p<0.01) and was accompanied by hyperinsulinemia (p<0.05) in the ApoE-/- and hypoadiponectinemia (p<0.01) in both mice strains. Although t-10, c-12 CLA supplementation increased plasma lipids and was associated with profound liver steatosis there was a reduction in atherosclerotic lesions in both mouse models (p<0.05). Analysis of mRNA and protein levels in the liver suggested that the differences in liver and plasma lipids may reflect inappropriate lipogenic response to t-10,c-12 CLA. In the high fat and fructose-fed hamster, the modulating role of fish fatty acids was investigated. The addition of DHA increased weight gain and adiposity compared to EPA and c-9, t-11 CLA supplementation. However, glucose tolerance was improved after 6 weeks of DHA supplementation (p? 0.01). Using [35S]methionine radiolabelling, DHA supplementation decreased apolipoprotein B100 synthesis and secretion. Newly synthesized cellular and secreted TG, as measured by [3H]glycerol incorporation, were also decreased with DHA supplementation. Although the effects of EPA were similar to those with DHA, the magnitude was generally lower. These results suggest that supplementation with fish fatty acids can improve several of the risk factors of the metabolic syndrome. Taken together, these observations indicate that some, but not all, bioactive fatty acids may be useful supplements for mediating cardiovascular risk factors.