Obesity starvation

On the basis of the resnlts with the obese, starvation can be divided arbitrarily into five phases the postabsorptive period, early starvation, intermediate starvation, prolonged starvation and, finally, the premortal period. Although these are characterised by different metabolic patterns, the transition from one period to another is gradnal. Some of the changes in the postabsorptive period and early starvation are described elsewhere in this book bnt they are bronght together in this chapter for completeness. 

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. 

Figure 2.2 Fat, or adipose, cells store extra energy from food. Adipose cells help insulate the body to keep it warm, cushion and protect the internal organs, and store extra energy for later use. When people consume more energy from food, the extra energy is stored as fat in adipose cells. Years ago, this stored energy could be used to avoid starvation in times of famine. Today, people never use this stored fat because famine does not exist in developed countries. These fat cells continue to accumulate and lead to weight gain and eventually to obesity.

The use of prolonged starvation for treatment of obesity has posed a fascinating problem that man is capable of fasting for periods of time beyond which he would have used all his carbohydrate resources and all his protein for gluconeogenesis in order to provide adequate calories as glucose for the central nervous system. 

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. 

There are some important differences between lean and obese snbjects in their responses to starvation. 

In lean subjects, amino acid oxidation, via glucose formation and glucose oxidation, provides almost four times more energy than in the obese snbjects (Table 16.4). That is, the obese lose protein mnch more slowly, which may be an important factor favouring survival of the obese in starvation. This is consistent with the fact that, from the data available, obese subjects have survived starvation approximately fonr times longer than the lean (abont 300 days versns 60-70 days Table 16.5). 

The plasma ketone body level increases twice as fast over live days starvation in lean snbjects compared with obese this may be an attempt by the body to restrict protein degradation in the lean by providing an alternative fnel to glucose for the brain as qnickly as possible. 

Tablel6.4 The contribution of amino acid oxidation to total energy reguirement during starvation in lean and obese subjects...

Table 16.5 Duration of starvation prior to death in lean and obese male adults...

In normal young children, the contribution of amino acid oxidation to energy requirement in starvation is about 1%, similar to that in the obese. In malnourished children, who have a protein-energy deficiency, it is even lower (4%). This suggests that a mechanism exists to protect muscle protein from degradation in children. Such a mechanism may involve a faster and greater increase in ketone body formation in children compared with adults (Chapter 7). 

This interlocking system of neuroendocrine controls of food intake and metabolism presumably evolved to protect against starvation and to eliminate counterproductive accumulation of fat (extreme obesity). The difficulty most people face in trying to lose weight testifies to the remarkable effectiveness of these controls. 

Glore, S. R., Layman, D. K. 4 Bechtel, P. J. (1984) Skeletal muscle and fat pad losses in male and female Zucker lean and obese rats after prolonged starvation. Nutr. Rep. Int. 29, 797-805. 

Let us pause to review the big picture. Normally, starvation results in low plasma leptin, while obesity results in increased plasma leptin. These two extremes in hormone concentrations provoke different responses by the hypothalamus Staiv ation in the normal mouse results in low plasma leptin, where low levels of leptin binding to the leptin receptor (in the hypothalamus) provoke a signal in the hypothalamus that results in Increases in neuropeptide Y. The hypothalamus Is a major site of production of the hormone, neuropeptide Y, Neuropeptide Y contains 36 ammo acids and has the following structure the one-letter abbreviations for the amino acids are used) ... 

Neuropeptide Y (NPY) is a potent appetite stimulant expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). It also inhibits thermogenesis. Repeated administration rapidly induces obesity. The ARC NPY neurones act homeostatically to correct negative energy balance. They are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones),... 

In addition to the types of food and drinks ingested, specific food-related situations will also influence plasma composition. They include vegetarianism, obesity, malnutrition, fasting, and starvation. 

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