Insulin resistance that is thought to be responsible for many of the metabolic changes that occur with the metabolic syndrome. In particular, insulin resistance is likely a primary driver of body fat accumulation. For example, insulin resistance has been shown to be associated with abdominal obesity, a condition whereby fat accumulates in the viscera of the abdomen. Obesity is also associated with high levels of plasma leptin. Leptin is a peptide hormone released by adipocytes, as an afferent signal to the hypothalamus, informing the central nervous system of the degree of adiposity in the body. In normal healthy individuals this afferent signal causes counterregulatory mechanism to lower body fat. In particular, the hypothalamus can decrease appetite and increase metabolic rate in response to high leptin levels. Leptin may therefore function as a lipostat. However, in the obese the hypothalamus becomes insensitive to the leptin signal and so the high leptin levels have little effect on rising body fat levels.
Individuals with insulin resistance are more likely to be obese compared to non-insulin resistant individuals. Further, the high levels of adiposity seen in obese individuals are associated with high levels of plasma leptin. It is often assumed that the high leptin levels are due to the presence of the high amount of adipose tissue. However, more recent evidence suggest that high levels of leptin may be caused by insulin resistance, independent to the degree of adiposity. For example, in one study1 researchers assessed the levels of adiposity, fasting leptin levels, fasting insulin levels and the degree of insulin resistance in a group of nondiabetic subjects. The results showed that the insulin stimulated uptake of glucose was significantly associated with the degree of insulin resistance but inversely associated with adiposity and fasting insulin levels. Adjustment to the data to take into account the degree of adiposity resulted in the the fasting plasma leptin levels remaining significantly associated with the insulin stimulated glucose uptake.
Therefore plasma insulin levels are associated with insulin resistance independent of the levels of adiposity. This may suggest that, like other metabolic dysfunctions present in the metabolic syndrome, the high circulating levels of leptin are caused by the presence of insulin resistance. For example, it has been suggested that insulin resistance is the cause of leptin resistance in the hypothalamus and that this causes leptin levels to rise in compensation. Alternatively high levels of circulating leptin may affect the insulin system, perhaps through modification of the amount of insulin released from the β-cells of the pancreas. Irrespective of the cause and effect of the relationship between leptin and insulin, it is clear that the metabolic syndrome and associated obesity is a highly complex metabolic disorder with multiple interacting systems. Simplifying obesity to a simple case of an energy imbalance is therefore disingenuous. Lowering high levels of leptin through reductions in insulin resistance is pivotal in reversing metabolic syndrome.
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