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

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 Delta-6 and Delta-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 omega-6 arachidonic acid (AA), omega-3 eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). EPA, DHA, and AA have negative feedback control on tumor necrosis factor-a and IL-6 synthesis. Hence, EPA, DHA, and AA deficiencies induced by an energy-dense diet increase generation of tumor necrosis factor-alpha 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-a and interleukin-6 enhance expression and activity of 11 beta-hydioxysteroid 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. (c) 2005 Elsevier Inc. All rights reserved.