Abdominal obesity, atheroslcerosis, insulin resistance, hyperlipidemias, hypertension, and type 2 diabetes mellitus are important components of metabolic syndrome X. An increase in pro-inflammatory cytokines, decrease in the concentrations of endothelial nitric oxide (eNO) and adiponectin, and an alteration in hypothalamic peptides that control satiety, hunger, and food intake have been reported in metabolic syndrome X. Although when and how metabolic syndrome X is initiated is not clear, there is evidence to suggest that increased consumption of high-energy diet, saturated and trans-fats by pregnant women and lactating mothers could trigger changes in the concentrations of long-chain polyunsaturated fatty acids (LCPUFAs) in maternal and fetal plasma and tissues. LCPUFAs have a modulatory influence on neuronal growth, maturation and synapse formation; influence the actions of hypothalamic peptides, neuropeptides, leptin, adiponectin, and various cytokines, especially during the perinatal period. In addition, LCPUFAs function as endogenous inhibitors of HMG-CoA reductase and ACE (angiotensin converting enzyme), augment eNO synthesis, modulate vascular tone, and potentiate insulin action both in the peripheral tissues and brain. Hence, sub-optimal maternal and fetal plasma and tissue concentrations of LCPUFAs increase pro-inflammatory cytokine levels that could trigger the development of metabolic syndrome X in those children who have a genetic predisposition, and continue to take highenergy diet, and saturated and trans-fats. This implies that perinatal interventions in the form of adequate supplementation of LCPUFAs could be of significant benefit in the prevention of metabolic syndrome X. Preliminary evidence suggests that supplementation of LCPUFAs can restore the levels of hypothalamic peptides to normal. In addition, weight loss due to Roux-en-gastric bypass procedure done in diet-induced obese animals decreased inflammation, restored hypothalamic “body weight/ appetite/ satiety set point” by restoring hypothalamic neuropeptides to normal, suggesting a cross talk between gastrointestinal hormones and hypothalamus. These evidences suggest that metabolic syndrome X occurs in a genetically predisposed subject as a result of interaction(s) between hypothalamic peptides, gastrointestinal tract, cytokines, nutrition, and life style factors.