The development of insulin resistance is a risk factor for the metabolic syndrome. Elevated levels of plasma fatty acids are associated with the development of insulin resistance, but the mechanisms are not fully understood. Fatty acids are taken up by muscle cells, but instead of being oxidised, they accumulate and then spill over into the circulation. The accumulating fatty acids then are converted to various signal molecules such as sphingolipids, phospholipids and eicosanoids. These then likely signal to the cell to desensitise the insulin receptor. It is known high quality diet, those that are nutrient dense but energy poor, are able to lower insulin resistance and improve blood glucose disposal to cells, perhaps by lowering fatty acid uptake to myocytes. However, less is known about how direct manipulation of the macronutrient content of the diet effects insulin resistance.
Researchers1 have investigated the effect of weight loss on insulin sensitivity by studying a group of 47 women following a hypocaloric diet. Half of the women took the drug orlistat (120 mg 3 times per day) while the other half took a placebo. The women had lost 8% of their body fat over a 3 to 6 month. Orlistat is an inhibitor of gastric lipase, and is estimated to inhibit fat absorption by 30% at the doses given. At baseline the groups were similar in terms of age, body weight, intraabdominal and subcutaneous fat and insulin sensitivity. Weight loss was similar between the two groups, and insulin sensitivity improved significantly in all women. Intraabdominal fat and subcutaneous fat decreased significantly in both groups, but only the orlistat group showed a decrease in the ration of intraabdominal fat to subcutaneous.
These results suggest that weight loss leads to in an increase in insulin sensitivity, but that reductions in fat absorption (intake) does not. This may be because hypocaloric intakes increase fat oxidation in muscle cells which reduces the accumulation of myocellular fatty acids. However, reductions in fat absorption (intake) does decrease the intraabdonimal fat to a greater extent than subcutaneous fat. In this study the blood pressure and blood lipids also improved similarly in both groups, suggesting that the weight loss had multiple beneficial effects. Interestingly the researchers also found that the proportion of dihomo-γ-linolenic acid (DGLA, C20:3 (n-6)) in the plasma phospholipids was inversely associated with the degree of insulin resistance in all women. This may suggests that the composition of the fatty acids in circulation has a strong influence on the likelihood of developing insulin resistance
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