Pathophysiology of metabolic syndrome X and its links to the perinatal period

Abstract

It is proposed that metabolic syndrome X is initiated in the perinatal period as a low-grade systemic inflammatory condition. Increased consumption of energy-dense diets by pregnant women and lactating mothers suppresses the activities of Δ-6 and Δ-5 desaturases not only in maternal tissues but also in fetal liver and the placenta, resulting in decreased plasma and tissue concentrations of long-chain polyunsaturated fatty acids ω-6 arachidonic acid (AA), ω-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-α and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-α and interleukin-6, markers of inflammation that in turn decrease production of endothelial nitric oxide and adiponectin to induce insulin resistance in maternal and fetal tissues. Increased concentrations of tumor necrosis factor-α and interleukin-6 enhance expression and activity of 11β-hydroxysteroid dehydrogenase type 1 enzyme, which produces abdominal obesity, insulin resistance, hyperlipidemia, hyperphagia, and hyperleptinemia, characteristic features of metabolic syndrome X. Continued consumption of an energy-dense diet in childhood aggravates these molecular events. This implies that supplementation of long-chain polyunsaturated fatty acids (especially AA, EPA, and DHA in appropriate ratios) from the perinatal period through adulthood could prevent, arrest, or postpone development of metabolic syndrome X.