Fatty acid during starvation

Hoskin, G. P., and Hoskin, S. P. (1977). Partial characterization of the heitiolymph lipids of Mercenaria mercenaria (Mollusca Bivalvia) by thin-layer chromatography and analysis of serum fatty acids during starvation. Biol. Bull. 152 373-381. 

Skeletal muscles, the heart, the liver, and many other tissues use fatty acids as their major fuel during fasting and other conditions that increase fatty acids in the blood. However, a number of other tissues (or cell types), such as the brain, use ketone bodies to a greater extent. For example, cells of the intestinal muscosa, which transport fatty acids from the intestine to the blood, use ketone bodies and amino acids during starvation, rather than fatty acids. Adipocytes, which store fatty acids in tri-acylglycerols, do not use fatty acids as a fuel during fasting but can use ketone bodies. Ketone bodies cross the placenta, and can be used by the fetus. Almost all tissues and cell types, with the exception of liver and red blood cells, are able to use ketone bodies as fuels. 

Inherited aldolase A deficiency and pyruvate kinase deficiency in erythrocytes cause hemolytic anemia. The exercise capacity of patients with muscle phos-phofiaictokinase deficiency is low, particularly on high-carbohydrate diets. By providing an alternative lipid fuel, eg, during starvation, when blood free fatty acids and ketone bodies are increased, work capacity is improved. 

Ketogenesis (Figure 6.19) occurs in the liver at most times but is greatly accelerated when acetyl-CoA production from p-oxidation of fatty acids exceeds the capacity of the TCA cycle to form citrate, that is during periods of starvation or in diabetics who have... 

During starvation or hypoglycaemia, the liver partially oxidises fatty acids to form ketone bodies, which are released and oxidised by the brain, intestine and the essential muscles (see below) (Figure 7.7). 

To provide an alternative fuel to glucose during starvation. Indeed, fatty acid oxidation restricts the rate of glucose utilisation, which maintains the blood glucose level, via a regulatory mechanism known as the glucose/ fatty acid cycle (Chapter 16). 

Figure 16.2 Redprocal relationship between the changes in the concentrations of glucose and fatty adds in blood during starvation in adult humans. As the glucose concentration decreases, fatty acids are released from adipose tissue (for mechanisms see Figure 16.4). The dotted line is an estimate of what would occur if fatty acid oxidation did not inhibit glucose utilisation. Such a decrease occurs if fatty acid oxidation in muscle is decreased by specific inhibitors.

Figure 16.8 Pattern of fuel mobitisatton and utUisatton during early starvation. This is starvation over a period of about 24 hours liver glycogen stores are nearly depleted and fatty acid mobilisation is taking place.

After 60 hours of starvation in lean subjects, fat utilisation (i.e. ketone bodies plus fatty acids) accounts for three-quarters of the energy expenditure (Table 16.1) a value which will rise even higher as starvation continues. Much of this increase is accounted for by hydroxybutyrate oxidation (the major ketone body) since, by 60 hours of starvation, the plasma concentration of hydroxybutyrate has increased 26-fold compared with a threefold increase in the concentration of fatty acid (the glucose concentration falls by less than 30%). By eight days of starvation there has been a sixfold increase in fatty acid concentration, whereas the concentration of hydroxybutyrate has increased about 50-fold (Table 16.2). The changes in these three major fuels in obese subjects during starvation for 38 days are shown in Figure 16.10. 

The administration of metabolizable vegetable oils as concentrated sources of nutrition has proved to be valuable for patients who are debilitated and who are unable to take nourishment orally. In addition, oils such as soy bean oil provide a source of essential fatty acids which can be rapidly depleted in a patient after starvation for only a few days. Wretlind and his colleagues devised the phospholipids-stabilized soy oil emulsion now marketed as Intralipid (Pharmacia, now Pfizer, New York, NY) in Sweden during the 1960s and this product has been modified to carry oil-soluble drugs such as diazepam. In Europe this is marketed as Diazemuls and it may be anticipated that other drugs may be presented in the same or similar vehicles. 

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... 

Ketone bodies (acetoacetate, /3-hydroxybutyrate, and acetone structures are presented in fig. 18.7) are made in the liver when /3 oxidation of fatty acids is in excess of that required by the liver. These water-soluble, energy-rich compounds are transported to other tissues for generation of energy. As we discuss later on, excess production of ketone bodies, that occurs during starvation or untreated diabetes, can be harmful. 

---