Oxidative stress is associated with insulin resistance. One of the possible drivers of oxidative stress is inflammation. Evidence shows that the obese have raised levels of inflammatory cytokines and chemokines in the plasma and in tissues. This may explain the low levels of antioxidants found in the obese because inflammation is a generator of free radicals and therefore oxidative stress. One of the possible causes of inflammation in the obese may be the presence of high levels of free fatty acids, which may activate the immune system and increase production of proinflammatory cytokines such as interleukins and tumor necrosis factors alpha (TNF-α). Evidence also suggests that monocyte chemotactic protein 1 (MCP-1) may be elevated in cases of obesity, perhaps through a free fatty acid stimulated mechanism, and this may cause the invasion of adipocytes by monocytes. The result of this invasion of bodyfat by the immune cells is proinflammatory, and such inflammation is well reported in obese individuals.
It is suspected that elevated levels of free fatty acids in tissues are the cause of the activated immune system in obese individuals. These fatty acids may originate partly from the de novo lipogenesis pathway, a pathway tasked with increasing fatty acid production from carbohydrate sources. However the production of free fatty acids is not thought to be high from this pathway as triglycerides are the main product. Alternatively, free fatty acid released from adipocytes may contribute significantly to total plasma levels under conditions of insulin resistance. This elevated plasma levels of free fatty acids may produce a state of low grade inflammation due to activation of pro-inflammatory cytokines. This low grade inflammation then may create oxidative stress and may significantly contribute to deterioration in insulin sensitivity that already exists through other aetiologies. The ability of antioxidants to reverse insulin sensitivity may be explained by their ability to reduce this oxidative stress induced insulin resistance.
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