Summary
Several types of experimental obesities are characterized by the occurrence of an early hypersecretion of insulin that produces an increase in both triglyceride secretion by the liver and fat deposition in adipose tissue. This hypersecretion of insulin, together with other ill-defined factors, is subsequently responsible for a state of insulin resistance.
The early oversecretion of insulin in hypothalamic and genetic (e.g. fa/fa rats) obesities can be experimentally demonstrated. Thus, within 20 min of acute lesion of the ventromedial hypothalamus (VMH), glucose-induced insulin secretion is greater in lesioned than in non-lesioned control rats; this increase can be blocked by superimposed, acute vagotomy. Moreover, an infusion of glucose to 17-day-old, pre-weaned control and genetically pre-obese rats (i.e. animals genetically-determined to become obese but with a normal body weight at this age) elicits much greater insulinaemia in the pre-obese than in the controls, despite similar basal, pre-infusion values in both. This increased insulin secretion in the pre-obese rats can be restored to normal by pre-treating them acutely with the cholinergic inhibitor, atropine. Thus, in these two types of obesity, an increased vagal tone appears to be of importance for the early occurrence of insulin over-secretion. Hyperinsulinaemia produced by increased tone of the vagus nerve appears to be reinforced by the decreased activity of the sympathetic system observed in obese rodents.
In many obese rodents, plasma growth hormone levels are abnormally low. The inadequate secretion of this hyperglycaemic hormone may explain why, in some types of obesity syndrome, hyperglycaemia is not necessarily present, despite insulin resistance.
Insulin resistance in experimental obesities has been shown to occur at the level of the adipose tissue, the muscles and more recently, the liver. The latter has been demonstrated using the in vivo euglycaemic clamp technique; thus, glycogenosis of genetically obese (fa/fa) rats could not be shut off, as in controls, by either basal or increased plasma insulin levels. This particular pathway is therefore insulin resistant.
The precise etiology of the early over-secretion of insulin in VMH-lesioned rats is, however, unknown; with VMH lesions, the origin is clearly the central nervous system (CNS), but the pathways actually interrupted by the lesions and those responsible for the hyperactivity of the vagus, remain to be determined. By analogy, it can be hypothesized that the cause of the early over-secretion of insulin in genetically obese rodents could also be in the CNS, though so far it has not been proven. This hypothesis is based on the observation that several CNS disorders arise in this type of obese rodent.
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Jeanrenaud, B. (1983). Energy Fuel and Hormonal Profile in Experimental Obesities. In: Mauron, J. (eds) Nutritional Adequacy, Nutrient Availability and Needs. Experientia Supplementum, vol 44. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-6540-1_5
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DOI: https://doi.org/10.1007/978-3-0348-6540-1_5
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