Lipogenesis insulin

Both dehydrogenases of the pentose phosphate pathway can be classified as adaptive enzymes, since they increase in activity in the well-fed animal and when insulin is given to a diabetic animal. Activity is low in diabetes or starvation. Malic enzyme and ATP-citrate lyase behave similarly, indicating that these two enzymes are involved in lipogenesis rather than gluconeogenesis (Chapter 21). 

Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg formation. In most mammals, glucose is the primary substrate for lipogenesis, but in ruminants it is acetate, the main fuel molecule produced by the diet. Critical diseases of the pathway have not been reported in humans. However, inhibition of lipogenesis occurs in type 1 (insulin-de-pendent) diabetes mellitus, and variations in its activity may affect the nature and extent of obesity. 

Insulin Also Regulates Lipogenesis by Other Mechanisms... 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

Lipogenesis is regulated at the acetyl-CoA carboxylase step by allosteric modifiers, phosphorylation/de-phosphorylation, and induction and repression of enzyme synthesis. Citrate activates the enzyme, and long-chain acyl-CoA inhibits its activity. Insulin activates acetyl-CoA carboxylase whereas glucagon and epinephrine have opposite actions. 

Analysis of lipid metabolism in adipocytes (insulin stimulation of lipogenesis) using a 60... 

Glucocorticoids inhibit the uptake of glucose by fat cells, resulting in increased lipolysis. The increased insulin secretion in response to hyperglycaemia also stimulates lipogenesis and ultimately increase in fat deposition. 

Glucocorticoids increase serum glucose levels and thus stimulate insulin release and inhibit the uptake of glucose by muscle cells, while they stimulate hormone sensitive lipase and thus lipolysis. The increased insulin secretion stimulates lipogenesis and to a lesser degree inhibits lipolysis, leading to a net increase in fat deposition combined with increased release of fatty acids and glycerol into the circulation. 

Endocrine Influences. A number of hormones are known to influence carbohydrate metabolism in the mammal. Insulin seems to increase oxidation of glucose, lipogenesis. and glycogenesis. Its primary mode of action may be io facilitate the entry of glucose into the cell. 

Insulin 2 Polypeptides (21 and 30 residues) Glucose uptake, lipogenesis, general anabolic effects... 

It has been reported also that epidermal growth factor stimulates fatty acid synthesis and the phosphorylation of ACC in rat liver and adipose tissues (Holland and Hardie, 1985) through phosphorylation of the I-peptide, suggesting that several peptide hormones sharing homology with insulin, such as IGF-1, could enhance lipogenesis similarly. 

Vestri, H., Maianu, L., Moellering, D., Garvey, W. (2007). Atypical antipsychotic drugs directly impair insulin action in adipocytes Effects on glucose transport, lipogenesis, and antilipolysis. Neuropsychopharmacology, 32, 765-772. 

Insulin is an antilipolytic hormone, and its effect on adipose tissue is to increase the transport of glucose into the fat cell, to stimulate lipogenesis and inhibit lipolysis. Thus, pyruvate dehydrogenase and acetyl-CoA carboxylase are activated, and the hormone-sensitive lipase is inactivated. In the normal, well-fed state insulin stimulates the deposition of fat. 

Taylor, W.M., D Costa, M., Angel, A., Halperin, M.L. (1977). Insulin-like effects of fluoroacetate on lipolysis and lipogenesis in adipose tissue. Can. J. Biochem. 55 982-7. 

---