Impact of polyunsaturated fatty acids on the development of metabolic syndrome and non-alcoholic fatty liver disease

Abstract

The implications of insulin resistance and imbalance of triglyceride metabolism play a pivotal role in the development of metabolic syndrome and its related illnesses. Adipose cells secrete various cytokines that interfere with insulin signaling pathways and decrease insulin sensitivity. In cases of obesity, this effect is often large enough to cause a systemic inflammation, which can lead to systemic insulin resistance. In cases of insulin resistance, insulin is unable to effectively lower blood glucose concentration and inhibit the hydrolysis and secretion of triglycerides (TG) in adipose tissue, resulting in hyperglycemia and hyperlipidemia (metabolic syndrome, MetS). The increased level of plasma TG results in higher uptake and storage of TG in the liver (hepatic steatosis) which may result in development of non-alcoholic fatty liver disease (NAFLD). N-3 Long chain polyunsaturated fatty acids (LCPUFA) and to a lesser extent n-6 LCPUFA counter this development in by three major processes: the increase of insulin sensitivity by increasing insulin receptor and GLUT4 expression in skeletal tissue cells, the down-regulation of lipogenesis mediated by lipogenic genes via suppresson of sterol regulatory element-binding protein-1 (SREBP-1) and carbohydrate responsive element-binding protein (ChREBP) and the up-regulation of fatty acid -oxidation mainly by activation of PPARα in the liver. Dietary intervention studies in humans, using fish oil capsules, have shown that n-3 LCPUFA doses of 2 – 4.2g daily are effective in lowering plasma TG levels in hyperlipidemic subjects by up to 40% and increasing insulin sensitivity. Studies in rats have further demonstrated that n-3 PUFA (primarily linolenic acid, C18:3 n-3 PUFA and oleic acid, C18:1 MUFA) administration was linked to decreased hepatic steatosis. Moreover, N-3 LCPUFA have been shown to improve NAFLD and its associated symptoms (e.g. hyperlipidemia) in humans. Considering the amount of dietary intervention studies in obese human subjects reporting the beneficial effects of n-3 LCPUFA on insulin sensitivity and plasma TG levels, n-3 LCPUFA may be essential to suppress the development and/or treat MetS. Hence, it may be advisable for obese individuals to include regular doses of n-3 LCPUFA in the diet as a measure to prevent or control MetS and MetS related diseases within the world population.