Fatty acids in the causation and therapy of metabolic syndrome.

The role of fatty acids in the prevention and pathogenesis of metabolic syndrome leading to cardiovascular diseases, type 2 diabetes and insulin resistance are reviewed. We did Medline, PubMed search till March, 2007. Excess of linoleic acid, trans fatty acids (TFA), saturated and total fat as well as refined starches and sugar are proinflammatory. Low dietary monounsaturated fatty acids (MUFA) and n-3 fatty acids and other long chain polyunsaturated fatty acids (LCPUFA) are important in the pathogenesis of metabolic syndrome. Sedentary behaviour in conjunction with mental stress and various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin that appear to be underlying mechanisms of obesity and metabolic syndrome. Excess secretion of these neurotransmitters in conjunction of underlying long chain PUFA deficiency, and excess of proinflammatory nutrients, may damage the neurons via proinflammatory cytokines, in the ventromedial hypothalamus and insulin receptors in the brain, especially during fetal life, infancy and childhood, resulting into their dysfunction. Since 30–50% of the fatty acids in the brain are LCPUFA, especially omega-3 fatty acids, which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may be protective. Omega-3 fatty acids are also known to enhance parasympathetic activity and increase the secretion of anti-inflammatory cytokines IL-4 and IL-10, as well as acetylecholine in the hippocampus. It is possible that marginal deficiency of LCPUFA, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus and infant, and also possibly in the child, adolescents and adults, may enhance oxidative stress and the release of proinflammatory cytokines; tumor necrosis factor-alpha, interleukin-1, 2 and 6 and cause neuronal and beta-cell dysfunction. Experimental studies indicate that ventromedial hypothalamic lesion in rats induces hyperphagia, resulting in glucose intolerance and insulin resistance. Administration of neuropeptide Y abolished the hyperphagia and ob mRNA (leptin mRNA) in these rats. Treatment with diets rich in MUFA and omega-3 fatty acids, meditation, beta blockers, ACE inhibitors, and phytochemicals may have a beneficial influence on insulin receptors and ventromedial hypothalamic dysfunction, causing beneficial effects in metabolic syndrome. Despite weaknesses, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids and MUFA rich foods may be applied to clinical practice and used to direct therapy for prevention of metabolic syndrome. Intervention trials with Columbus diet and lifestyle in patients with metabolic syndrome would be necessary to provide a proof for our statement.