The body possesses a complex feedback mechanisms to ensure adequate energy intake. This feedback mechanisms is located mainly in the hypothalamus and involves neuronal and hormonal mechanisms. Evidence is accumulating that it is a dysfunction in this system that is the causative factor in weight gain and obesity. Therefore obesity can be considered a product of metabolic dysfunction, and as such should be classified as any other disease. For this reasons the old paradigm that obesity is simply caused by eating too much food or performing too little exercise is shown to be erroneous and based on outdated evidence. One of the main advances in the understanding of obesity as a disease is the further clarification that insulin resistance plays a pivotal role in its formation. Insulin resistance is a condition whereby the cells of the body become desensitised to insulin and as a result blood glucose levels rise. However, it is now understood that the hypothalamus also becomes desensitised to insulin.
Under normal healthy conditions insulin enters the brain and acts within receptors of the brain to induce satiety. It has been shown that interaction between insulin and the insulin receptors within the central nervous system are pivotal at decreasing subsequent food intake. This makes sense physiologically because insulin is released in response to food intake and there would be a requirement to reduce subsequent energy intakes postprandially. The main targets of insulin within the brain are located within the hypothalamus. Animal studies have confirmed that transport systems exist for the passage of insulin into the brain, and that direct administration of insulin causes a reduction in appetite. In addition, insulin may induce thermogenesis, which is initiated through a firing of sympathetic neurons to brown adipose tissue. However, insulin induced hypoglycaemia is able to override the centrally mediated effects of insulin to facilitate rapid food intake, and this is an important defence against hypoglycaemic induced coma.
The desensitisation of the hypothalamus to the action of insulin is therefore problematic as it truncates this important signal pathway that regulates energy homeostasis. When insulin levels rise they should curtail further food intake and thus prevent overeating. However desensitisation of the hypothalamus to the action of insulin diminishes this effect. In addition, the stimulation of thermogenesis is also reduced and this further derailed homeostatic energy balance. The result of insulin desensitisation in the hypothalamus is further compounded by the fact that a secondary leptin resistance also develops and this is problematic because leptin is an afferent signal to inform the hypothalamus as to the current levels of body fat. Without this signal from letim, the information is not available and so energy expenditure and intake cannot be adjusted to compensate for increases in adiposity. Interestingly, fructose does not stimulate the release of insulin and so automatically bypasses this important energy regulatory system.
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