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Lipids Metabolism

Although lipids are essential for homeostatsis and many aspects of reproduction, organ and cellular physiology, they are also linked to pathological processes such as obesity, diabetes and the metabolic syndrome. Some key players are apoliproteins, C-reactive proteins (C-RPs), fatty acid binding proteins (FABPs), fatty acid synthase (FAS) and spingosine-1-phosphate (S1P). Apolipoproteins comprise several major classes labeled alphabetically and their subclasses designated with specific numbers (e.g. ApoA1, ApoA2, ApoA3, etc.). The ratio of ApoB (primarily LDL) to ApoA1 (HDL-C) is a good indicator of cardiovascular risk. FABPs are expressed in a tissue-specific manner and shuttle fatty acids to cellular compartments. Some have important roles in regulating metabolism such as adipocyte FABP (aP2) which can affect insulin sensitivity, lipid metabolism and is involved in atherosclerosis.
An important inflammatory marker, C-RP, is mainly synthesized in the liver though it is also produced in atherosclerotic lesions, the kidney, neurons, and alveolar macrophages. Its physiological role is to bind to phosphatidylcholine expressed on the surface of dead or dying cells (and some bacteria) in order to activate the complement system via the C1Q complex. Hepatic C-RP synthesis is stimulated by the adipokines leptin and IL-6 and down-regulated by adiponectin. C-RP has been shown to impair insulin signaling and contributes to atherothrombosis. Synthesis of fatty acid (de novo) is due to the sole mammalian enzyme, FAS, whose gene expression in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, IL-6, leptin and RBP4. In addition, FAS is highly expressed in most human carcinomas and is associated with poor prognosis in breast and prostate cancer. FAS and fatty acid metabolism in cancer has become a focus for the potential diagnosis and treatment of cancer. S1P is a signaling sphingolipid, also referred to as a bioactive lipid mediator. S1P resides normally on lipoproteins, particularly HDL, and albumin in the circulation. Collective data appears to identify a novel role for sphingolipids in contributing to the prothrombotic and proinflammatory phenotype of the obese adipose tissue currently believed to play a major role in the pathogenesis of obesity-mediated cardiovascular and metabolic disease.

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