Omega-3 fatty acids and metabolic syndrome: Effects and emerging mechanisms of action

Epidemiological, human, animal, and cell culture studies show that n3 fatty acids, especially alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n3 and n6 fatty acids as well as the interactions of n3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n3 fatty acids to reduce the risk factors of metabolic syndrome. (Authors abstract)

This extensive review describes the beneficial roles that n3 polyunsaturated fatty acids (PUFA) can play in reducing metabolic syndrome (MS). MS is defined as the clustering of interrelated risk factors for cardiovascular disease and type 2 diabetes, including hyperglycemia, insulin resistance, hypertension, hypertriglyceridemia, decreased HDL-cholesterol concentration, and obesity.  The cardioprotective effects of n3 fatty acids, especially alpha linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), have been defined by epidemiological, human, animal, and cell culture studies. The paper provides an overview of the metabolism of n3 and n6 series of fatty acids. The beneficial effects of n3 fatty acids on risk factors of metabolic syndrome are reviewed including in the areas of adiposity and dyslipidemia;  glucose homeostasis and insulin resistance; hypertension; oxidative stress and inflammation. Several concepts are described. There is growing consensus that the anti-inflammatory effects of n3 fatty acids are mainly mediated by displacing the pro inflammatory n6 fatty acid pathway. It is also possible that the lipid-lowering effects of n3 fatty acids could also result in improved glucose handling, reduced blood pressure and oxidative stress.  Oxidative stress and inflammation are key and inter-related indications in obesity and metabolic syndrome. From the limited available data, physiological responses to ALA differ from EPA and DHA primarily in lipid handling. ALA reduced LDL cholesterol whereas EPA and DHA increased HDL cholesterol concentrations with increased cardiac and hepatic lipoprotein/ TAG lipases. Most of the responses to all three n3 PUFA remain comparable, probably with closely associated mechanisms of action in insulin resistance, hypertension, and inflammation. More studies need to be implemented with ALA, EPA and DHA to differentiate their effects.  The authors notes that more focused studies with each of the three n3 fatty acids are required to draw firm conclusions on the mechanisms of action of the individual fatty acids. Also, inter species genetic and metabolic variations have to be carefully
considered for animal studies to ensure reliability and reproducibility of the results in humans. (Editors comments)