Lipogenesis in adipose tissue

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. 

Although the effects of insulin on postprandial metabolism are profound, other factors (e.g., substrate supply and allosteric effectors) also affect the rate and degree to which these processes occur. For example, elevated levels of fatty acids in blood promote lipogenesis in adipose tissue. Regulation by several allosteric effectors further ensures that competing pathways do not occur simultaneously for example, in many cell types fatty acid synthesis is promoted by citrate (an activator of acetyl-CoA carboxylase), whereas fatty acid oxidation is depressed by malonyl-CoA (an inhibitor of carnitine acyltransferase I activity). The control of fatty acid metabolism is described in Section 12.1. 

Ohminami, H., Y. Kimura, H. Okuda, T. Tani, S. Arichi, and T. Hayashi Effects of Ginseng Saponins on the Actions of Adrenalin, ACTH and Insulin on Lipolysis and Lipogenesis in Adipose Tissue. Planta Medica 41, 351 (1981). 

As shown in a Swedish cohort of healthy 50-year-old men with 20 years follow-up, proportion of 14 0 and 16 0 in serum cholesterol esters predicted the development of metabolic syndrome, independently of other metabolic and lifestyle factors [105]. Besides serum lipids, proportion of PA in adipose tissue is also related to insulin sensitivity. Unlikely 14 0 and 18 0, which were positively associated with insulin sensitivity, PA inversely correlated with insulin sensitivity in 59 healthy British men and women [134]. Since the authors excluded the effect of dietary intake for any of these SFA, they concluded that the reason is de novo lipogenesis in adipose tissue. In human skeletal muscle phospholipids, SFA [135,135] and especially PA [137] have been negatively associated with insulin sensitivity and Type 2 diabetes, [138] which could partly reflect dietary intake [139], In a Finnish cohort study of 4 years follow-up, impaired fasting glucose and Type 2 diabetes incidence were associated with serum nonesterified 16 0 levels, but were not associated with baseline dietary 16 0 intakes assessed from dietary records [140], Recently published prospective follow-up study showed that erythrocyte membrane fatty acids nominaly predict incident type 2 diabetes [141], In the American Atherosclerosis Risk in Commimities (ARIC) study, 2909 middle-aged men and women were followed for 9 years. The incidence of Type 2 diabetes was associated with total SFA levels of plasma cholesterol esters (also observed for 16 0 independently) and phospolipids (also for 16 0 and 18 0) [101]. In a more recent 4-year case-... 

Roberts R, Hodson L, Dennis AL et al. Markers of de novo lipogenesis in adipose tissue associations with small adipocytes and insulin sensitivity in humans. Diabetologia. 2009,52 882-890. 

In addition to stimulating corticosteroidogenesis in the adrenals, ACTH also stimulates lipogenesis in adipose tissue and the release of ascorbic acid from the adrenals. 

Only in the 1960 s was it established that peripheral tissue, such as heart and kidney, could actively metabolize ketone bodies to use as respiratory fuel. In fact, glucose and fatty acids complement each other as respiratory fuels. Consequently, when glucose is low (starvation or ketosis in cattle) or unavailable (diabetes), glucagon is secreted, inducing lipogenesis in adipose tissue with liberation of free fatty acids. 

There is other evidence that milk energy output is decreased when acetate forms less than 0.5-0.55 and propionate more than 0.35-0.45 of the rumen volatile fatty acids. This is thought to be the result of a reorientation of metabolism towards increased lipogenesis in adipose tissue and decreased lipogenesis in the mammary gland. 

There are no reliable data available regarding the exact proportion of dietary carbohydrate which is converted to triglycerides in the liver lipogenesis in adipose tissue is probably quantitatively much more important under normal circumstances (Shapiro 1957). As far as is known, no lipoprotein glyceride is liberated from adipose tissue into the plasma. 

Ohminami H, Kimura Y, Okuda H, Tani T et al. 1981 Effects of ginseng saponins on the actions of adrenaline, ACTH and insulin on lipolysis and lipogenesis in adipose tissue. Planta Med 41 351-358... 

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 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... 

In adipose tissues, insulin accelerates the dissimilation of glucose to CO2 through the Embden-Meyerhof pathway and the hexose monophosphate shunt and increases its utilization for glycogen and fatty acid synthesis. Insulin is without effect on fatty acid uptake and lipogenesis when glucose is absent from the medium. And the studies of Fain and Loken [132] have established that the antilipolytic effect of insulin is blocked by trypsin. Trypsin does not affect its inhibition through other metabolic interferences. A protein factor, possibly a receptor, probably is needed for insulin s action on adipose tissue. 

Hepatic lipogenesis from tritiated H20 was studied in perfused rat liver the rate of hepatic synthesis was 7 /Amoles/per gram of liver per hour (Windmueller and Spaeth, 1966). This value is one-half of the synthesis observed in liver slices (Foster and Bloom, 1963) and adipose tissue (Katz et al., 1965 Landau and Katz, 1965 Katz and Rognstad, 1966). In the in vivo experiments where H20 was injected intraperitoneally, the radioactivity recovered in both hepatic and carcass fatty acids was considerably lower, i.e., 0.001 and 0.009%, respectively, of the dose administered. The results obtained in vitro with rat adipose tissue show that, in the presence as well as in the absence of insulin, 2 hydrogen atoms from H2O are incorporated for each C2 unit of fatty acids. Quantitatively, this incorporation is of the same order as that found in vivo (0.0034% of the dose present in the incubation medium) (Landau and Katz, 1965). H is also present on the odd atoms of fatty acids in adipose tissue (Foster and Katz, 1966 Jungas, 1968) and liver slices (Foster and Bloom, 1963). 

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