Lipogenesis

Lipogenesis is the metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. The triglycerides in fat are packaged within cytoplasmic lipid droplets. The process begins with acetyl-CoA, which is an organic compound used to transfer energy from metabolism of carbohydrates, fatty acids, and ethanol. Through the citric acid cycle, acetyl-CoA is broken down to produce ATP, which is then an energy source for many metabolic processes, including protein synthesis and muscle contraction. Lipogenesis is the metabolic process through which acetyl-CoA is converted to triglyceride for storage in fat. The triglycerides in fat are packaged within cytoplasmic lipid droplets. The process begins with acetyl-CoA, which is an organic compound used to transfer energy from metabolism of carbohydrates, fatty acids, and ethanol. Through the citric acid cycle, acetyl-CoA is broken down to produce ATP, which is then an energy source for many metabolic processes, including protein synthesis and muscle contraction. Lipogenesis encompasses both fatty acid and triglyceride synthesis, with the latter being the process by which fatty acids are esterified to glycerol before being packaged into very-low-density lipoprotein (VLDL). Fatty acids are produced in the cytoplasm of cells by repeatedly adding two-carbon units to acetyl-CoA. Triglycerides, on the other hand, are produced in the endoplasmic reticulum of cells by bonding three fatty acid molecules to a glycerol molecule. Both processes take place mainly in liver and adipose tissue. After being packaged into VLDL, the resulting lipoprotein is then secreted by the liver directly into the blood for delivery to peripheral tissues. Fatty acid synthesis starts with acetyl-CoA and builds up by the addition of two-carbon units. Fatty acid synthesis occurs in the cytoplasm of cells while oxidative degradation occurs in the mitochondria. Many of the enzymes for the fatty acid synthesis are organized into a multienzyme complex called fatty acid synthase. The major sites of fatty acid synthesis are adipose tissue and the liver. Triglycerides are synthesized by esterification of fatty acids to glycerol. Fatty acid esterification takes place in the endoplasmic reticulum of cells by metabolic pathways in which acyl groups in fatty acyl-CoAs are transferred to the hydroxyl groups of glycerol-3-phosphate and diacylglycerol. Three fatty acid chains are bonded to each glycerol molecule. Each of the three -OH groups of the glycerol reacts with the carboxyl end of a fatty acid chain (-COOH). Water is eliminated and the remaining carbon atoms are linked by an -O- bond through dehydration synthesis. Both the adipose tissue and the liver can synthesize triglycerides. Those produced by the liver are secreted from it in the form of very-low-density lipoproteins (VLDL). VLDL particles are secreted directly into blood, where they function to deliver the endogenously derived lipids to peripheral tissues. Insulin is a peptide hormone that is critical for managing the body's metabolism. Insulin is released by the pancreas when blood sugar levels rise, and it has many effects that broadly promote the absorption and storage of sugars, including lipogenesis. Insulin stimulates lipogenesis primarily by activating two enzymatic pathways. Pyruvate dehydrogenase (PDH), converts pyruvate into acetyl-CoA. Acetyl-CoA carboxylase (ACC), converts acetyl-CoA produced by PDH into malonyl-CoA. Malonyl-CoA provides the two-carbon building blocks that are used to create larger fatty acids. Insulin stimulation of lipogenesis also occurs through the promotion of glucose uptake by adipose tissue. The increase in the uptake of glucose can occur through the use of glucose transporters directed to the plasma membrane or through the activation of lipogenic and glycolytic enzymes via covalent modification. The hormone has also been found to have long term effects on lipogenic gene expression. It is hypothesized that this effect occurs through the transcription factor SREBP-1, where the association of insulin and SREBP-1 lead to the gene expression of glucokinase. The interaction of glucose and lipogenic gene expression is assumed to be managed by the increasing concentration of an unknown glucose metabolite through the activity of glucokinase. Another hormone that may affects lipogenesis through the SREBP-1 pathway is leptin. It is involved in the process by limiting fat storage through inhibition of glucose intake and interfering with other adipose metabolic pathways. The inhibition of lipogenesis occurs through the down regulation of fatty acid and triglyceride gene expression. Through the promotion of fatty acid oxidation and lipogenesis inhibition, leptin was found to control the release of stored glucose from adipose tissues.