Metabolic syndrome may be a disease of the brain related to Western diet-induced proinflammatory damage of the arcuate nucleus and POMC neurons in the brain, as well as to damage of beta cells in the pancreas. Consumption of a Western diet and eating late at night can double the adverse effects of diet by causing systemic inflammation and damage to the circadian clock machinery, leading to circadian disruption, resulting in metabolic syndrome due to low melatonin and leptin and high cortisol and ghrelin. These neurotransmitters are known to increase oxidative stress, which may damage certain areas of the brain, endothelial cells, and myocardial cells via subcellular remodeling. Increases in free radicals may damage other neurons, macrophages, hepatocytes in the liver, β-cells in the pancreas, and endothelial cells and smooth muscle cells, due to the release of proinflammatory cytokines. Pro-inflammatory cytokines, in conjunction with an underlying deficiency of long-chain PUFA, CoQ10, and polyphenolics, and excess of omega-6-fatty acids, may damage cells in various organs, including pancreatic β-cells, resulting in a further increase in insulin resistance, metabolic syndrome, and diabetes mellitus. © 2018 Nova Science Publishers, Inc. All rights reserved.