Triacylglycerol/fatty acid cycle

The hormone leptin, which is secreted by adipose tissue, is considered to play a role in the control of the amount of triacylglycerol in adipose tissue by decreasing appetite and by increasing energy expenditure. Leptin increases the rate of the triacylglycerol fatty acid cycle (Chapter 15). 

In addition to the increased mobilisation of fatty acids, there is an increase in the rates of cycling in the intra- and inter-cellular triacylglycerol/fatty acid cycles that contribute to increased energy expenditure in trauma. 

Substrate cycling (e.g. the Cori cycle and the intra- and inter-cellular triacylglycerol/fatty acid cycles (Chapter 3)) in which there is no net metabolic change so that the energy from ATP hydrolysis is released as heat. 

Figure 21.21 Diagram to illustrate the intertissue triacylglycerol/ fatty acid cycle, (i) Fatty acids released from adipose tissue are esterified in the liver, (ii) The triacylglyceral is released in the form of VLDL. (iii) The triacylglycerol in the latter is hydrolysed in the capillaries in the adipose tissue. Some fatty acids are taken up by adipose b ssue, but about 30% are release in the circulation that give life to the extracellular cycle. The intracellular cycle exists in the adipocytes.

The free fatty acids formed by lipolysis can be reconverted in the tissue to acyl-CoA by acyl-CoA synthetase and reesterified with glycerol 3-phosphate to form triacylglycerol. Thus, there is a continuous cycle of lipolysis and reesterification within the tissue. However, when the rate of reesterification is not sufficient to match the rate of lipolysis, free fatty acids accumulate and diffuse into the plasma, where they bind to albumin and raise the concentration of plasma free fatty acids. 

Heart Pumping of blood Aerobic pathways, eg, P-oxidation and citric acid cycle Free fatty acids, lactate, ketone bodies, VLDL and chylomicron triacylglycerol, some glucose Lipoprotein lipase. Respiratory chain well developed. 

Two conditions in which the rate of ketone body formation is increased are hypoglycaemia and prolonged starvation in adults or short-term starvation in children. What is the mechanism for increasing the rate Although there are several fates for fatty acids in the liver, triacylglycerol, phospholipid and cholesterol formation and oxidation via the Krebs cycle, the dominant pathway is ketone body formation (Figure 7.20). Three factor regulate the rate of ketone body formation (i) hormone sensitive lipase activ-... 

Examples of a substrate cycles are the glucose/glucose 6-phosphate, fructose 6-phosphate/fmctose 1,6-bisphosphate and fatty acid/triacylglycerol cycle. These are described in Chapters 3, 6, 7 and 11. One study has shown a direct role of a substrate cycle in heat generation (Appendix 9.11). 

Figure 9.29 Control of heat production in brown adipose tissue. Catecholamines increase cyclic AMP concentrab on which stimulates triacylglycerol lipase which increases the long-chain fatty acid level, which increases the fluxes through P-oxidation and the Krebs cycle, and the activity of the uncoupling protein. Uncoupling decreases the ATP concentration which further increases the activity of the uncoupling.

It increases the release of fatty acids from adipose tissue which raises the plasma level of long-chain fatty acids, to provide a fuel for muscle, if it becomes physically active (Chapter 13). It also increases the cycling between triacylglycerol and fatty acids in adipose tissue. 

Fig. 21-20 see also Fig. 17-1). Flux through this tri-acylglycerol cycle between adipose tissue and liver may be quite low when other fuels are available and the release of fatty acids from adipose tissue is limited, but as noted above, the proportion of released fatty acids that are reesterified remains roughly constant at 75% under all metabolic conditions. The level of free fatty acids in the blood thus reflects both the rate of release of fatty acids and the balance between the synthesis and breakdown of triacylglycerols in adipose tissue and liver. 

The function of the apparently futile triacylglycerol cycle (futile cycles are discussed in Chapter 15) is not well understood. However, as we learn more about how the triacylglycerol cycle is sustained via metabolism in two separate organs and is coordinately regulated, some possibilities emerge. For example, the excess capacity in the triacylglycerol cycle (the fatty acid that is even-... 

Features an important new section on glyceroneogenesis and the triacylglycerol cycle between adipose tissue and liver, including their roles in fatty acid metabolism (especially during starvation) and the emergence of thiazolidinediones as regulators of glyceroneogenesis in the treatment of type II diabetes... 

The major source of free fatty acids in the blood is from the breakdown of triacylglycerol stores in adipose tissue which is regulated by the action of hormone-sensitive triacylglycerol lipase (see Topic K4). Fatty acid breakdown and fatty acid synthesis are coordinately controlled so as to prevent a futile cycle (see Topic K3). 

The anabolic hormone insulin has the opposite effect to glucagon and epinephrine. It stimulates the formation of triacylglycerols through decreasing the level of cAMP, which promotes the dephosphorylation and inactivation of hormone-sensitive lipase (Fig. 5). Insulin also stimulates the dephosphorylation of acetyl CoA carboxylase, thereby activating fatty acid synthesis (see Topic K3). Thus fatty acid synthesis and degradation are coordinately controlled so as to prevent a futile cycle. 

Fats are catabolised by hydrolysis to free fatty acids and glycerol. Tbe free fatty acid is metabolised in the liver and peripheral tissue via /S-oxidation into acetyl CoA acetyl-CoA then enters the TCA cycle. Glycerol is used by the liver for triacylglycerol synthesis or for gluconeogenesis (following its conversion to 3-phosphoglycerate). 

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