1. Hypercholesterolemia: a disease of the brain

Abstract

Cholesterol, an important physiological factor becomes atherogenic only when it is oxidized. All the risk factors such as Western diet, sedentary behavior, tobacco, pollutants, diabetes have the ability to increase and oxidize the cholesterol in our body which results in to atherothrombosis. Cholesterol is also important for the synthesis of steroids and steroid hormones, and for the bile and bile acid salts. Sterol plays also an important role in embryonic development. Recent evidence indicates that cholesterol homeostasis in the central nervous system has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. Recently cholesterol has been indicated to maintain the cell membrane integrity of the epithelial cells of the beta cells of pancreas, which is helpful in the prevention of diabetes among patients receiving statins. In neuronal cell membrane phospholipids, it maintains the integrity of neurons and prevents depression and aggression among patients receiving hypocholesterolemic agents. Increased production of cholesterol has to be avoided because it forms solid crystals which are known to kill normal cells. Increased cholesterol in the tissues may also have adverse effects because if it is oxidized, it predisposes inflammation in the arteries and deposits in arteries, initiating atherosclerosis. Therefore regulation of cholesterol metabolism is achieved predominantly through repression of transcription of genes that govern the synthesis of cholesterol and its receptor-mediated uptake from plasma lipoproteins via low-density lipoprotein cholesterol receptors in the hepatocytes and macrophages. Hypercholesterolemia could be a function of the brain due to a disturbance in the central circadian clock, causing disturbed circadian energy metabolism. Psychological stress can also cause hypercholesterolemia, yet the pathophysiological mechanisms involved remain elusive. The macrophage-specific reverse cholesterol transport, by which the transfer of cholesterol from macrophage foam cells to liver and feces is completed, appears to be an important antiatherogenic pathway which is blocked due to mental stress resulting in to hypercholesterolemia. Studies link energy homeostasis to the circadian clock at the behavioral, physiological, and molecular levels, emphasizing that certain nutrients and the timing of food intake may play a significant role in the development of dyslipidemia and obesity with greater risk of cardiovascular diseases and type 2 diabetes including hypercholesterolemia. In brief, it is possible that autonomic dysfunction due to diet and lifestyle factors, mental stress and disturbance in the central circadian clock can contribute in the development of hypercholesterolemia as a function of the brain.