The metabolic syndrome is a cluster of metabolic dysfunctions characterised by central and peripheral insulin resistance. Insulin resistance is a condition whereby the cells of the body become insensitive to the action of insulin and as a result less of the glucose is able to pass from the blood to the cells. This causes the blood glucose levels to rise and in response the pancreas releases more insulin to drive down blood sugar levels. As a result fasting insulin and fasting glucose levels rise. One of the main problems with this situation is that insulin is an anabolic hormone and increases in the plasma insulin levels during the fasting period, a time when normally glucagon would dominate, causes inhibition of catabolic pathways that are used to oxidise energy. This may be one of the main drivers of the weight gain seen in those individuals with insulin resistance. Once insulin resistance has developed, exaggerated responses to glucose ingestion occur and this can be measured using an oral glucose tolerance test.
However, it has also been observed that obese individuals also show exaggerated responses to dietary fat. This results in higher concentrations of triglycerides over the postprandial period when compared to non-obese subjects. Increases in plasma triglycerides postprandially are associated with increases in markers for inflammation, and fatty acids may therefore be a contributory factor in the systemic inflammation and oxidative stress seen in obese individuals. It has also been observed that the type of fatty acids provided by a meal can also influence that amount of inflammation. In particular, the ratio of omega-3 to omega-6 fatty acids is a major determinant of the postprandial inflammatory response. A number of studies have measured the inflammatory markers following a high fat meal and results from these studies seem to suggest that interleukin-6 concentrations, but not C-reactive protein concentrations, rise following a high fat meal in obese individuals.
The postprandial inflammatory responses to high fat meals may be linked to insulin resistance because insulin sensitive individuals display much lower inflammatory responses compared to insulin insensitive individuals. This adds further weight to the hypothesis that insulin resistance drives the metabolic dysfunction to energy homeostasis, appetite regulation, and the major biochemical pathways, that is seen in the metabolic syndrome. The high levels of inflammation and oxidative stress seen in obese insulin resistant individuals may also explain the poor antioxidant status observed in obesity. Fatty acid and glucose pathways are interlinked biochemically and so it should be no surprise that disruption to the glucose system through development of insulin also disrupts fatty acid metabolism and causes changes to the regulation of plasma triglycerides. Insulin of course in its role as an anabolic hormone controls many of the lipid pathways through its allosteric action on key regulatory enzymes.
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