Liver Starvation

A similar lack of adverse effects of halothane has been found in liver tissue metabolic intermediates in animals fed a high fat diet, or animals starved for 24 hours (Biebuyck and Lund, 1972). Thus, situations in which a high concentration of fatty acids is available to the liver (starvation or exogenous administration), appear to have a protective effect against metabolic changes bought about by halothane. 

The first hormonal signal found to comply with the characteristics of both a satiety and an adiposity signal was insulin [1]. Insulin levels reflect substrate (carbohydrate) intake and stores, as they rise with blood glucose levels and fall with starvation. In addition, they may reflect the size of adipose stores, because a fatter person secretes more insulin than a lean individual in response to a given increase of blood glucose. This increased insulin secretion in obesity can be explained by the reduced insulin sensitivity of liver, muscle, and adipose tissue. Insulin is known to enter the brain, and direct administration of insulin to the brain reduces food intake. The adipostatic role of insulin is supported by the observation that mutant mice lacking the neuronal insulin receptor (NDRKO mice) develop obesity. 

Nilsson, L.H. Hultman, E. (1973). Liver glycogen in man. The effect of total starvation or a carbohydrate-poor diet followed by carbohydrate refeeding. Scand. J. Clin. Lab. Invest. 32, 325-330. 

In the liver, it forms ketone bodies (acetone, ace-toacetate, and 3-hydroxybutyrate) that are important fuels in prolonged starvation. 

Six compounds have vitamin Bg activity (Figure 45-12) pyridoxine, pyridoxal, pyridoxamine, and their b -phosphates. The active coenzyme is pyridoxal 5 -phos-phate. Approximately 80% of the body s total vitamin Bg is present as pyridoxal phosphate in muscle, mostly associated with glycogen phosphorylase. This is not available in Bg deficiency but is released in starvation, when glycogen reserves become depleted, and is then available, especially in liver and kidney, to meet increased requirement for gluconeogenesis from amino acids. 

Starvation stimulates the consumption of glycogen reserves in liver... 

Starvation elicits mobilization of triglycerides from the adipose tissue and inhibits the endogenic cholesterol synthesis owing to the low activity of hydroxy-methylglutaryl-CoA reductase. The latter process provides the possibility for the active production of ketone bodies in the liver. 

Many tissues (muscle, liver, renal cortex) prefer fat for an energy supply, at least in the resting state. The exception is red blood cells and brain. These tissues depend heavily on glycolysis for energy. Red cells cannot survive without glucose (no mitochondria), but during prolonged starvation, brain can adapt to utilize fat metabolites produced by the liver (ketone bodies). 

Glycogen stores in liver and kidney are exhausted in about 24 hours. After this, the body must find glucose equivalents somewhere. The major metabolic adaptations of starvation are the result of having to maintain glucose levels without any direct source of it (Fig. 17-8). 

KETONE BODIES are generated by the liver and used by muscle and brain (after adaptation during starvation). 

Elevated metallothionein levels are not necessarily indicative of heavy-metal insult. Starcher et al. (1980) show that liver metallothionein levels in mice are elevated following acute stress or starvation, and that this effect is blocked by actinomycin D, a protein synthesis inhibitor. It is further emphasized that not all zinc-binding proteins are metallothioneins (Webb etal. 1985 ... 

Investigations of changes in G-6-PDH activity of liver cells in starving rats resulted in the finding of reduced activity (A3) depending on the duration of the starvation period (W10). 

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... 

If food is unavailable for more than approximately 24 h, glycogen reserves in the liver will become depleted and the individual would enter a state of biochemical starvation. Progressive loss of muscle protein (wasting) would occur in order to generate sufficient glucose to maintain the metabolic activity of, in particular, the central nervous system. 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

Another, perhaps less dramatic condition, is the effect of social drinking after a very short period of starvation. A period of eating a high protein, low carbohydrate meal for several days, followed by a missed breakfast and a late lunch might result in a low level of liver glycogen. If now, lunch is preceded by alcoholic drinks, hypoglycaemia could readily develop, and, if severe, could lead to coma with possible... 

In this book it is suggested that one possible cause of death in prolonged starvation is severe hypoglycaemia. This may be due to a lack of amino acid precursors since almost all the body protein has been broken down. Alternatively, the fat store in the body has been totally depleted, so that the plasma fatty acid level will be close to zero. Consequently, there will be no fatty acid oxidation in the liver and therefore little or no ATP generation to support gluconeogenesis. Post-mortem studies on individuals who have died of starvation show that the fat stores are totally depleted. This topic is discussed further in Chapter 16. 

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