Obesity is know to be a risk factor for cardiovascular disease. However, obesity is complex and its aetiology is not fully understood. It is known that a positive energy balance in addition to development of the metabolic syndrome (syndrome X) are major contributory factors to obesity because they are characterised by insulin resistance. Insulin resistance is generally considered to lead to systemic changes that result in a pro‑inflammatory environment. Fatty acids in the plasma of obese subjects are elevated, and it is suspected that the raised levels of circulating fatty acids are a major cause of this inflammation. Systemic inflammation may then lead to damage to the endothelium of blood vessels, this effect being exacerbated by the high blood glucose levels that causes the formation of advanced glycation end products by cross reaction with proteins.
Insulin itself may contribute to this vascular inflammation by increased gene expression of a number of inflammatory immune proteins such as MCP-1, VCAM-1 and macrophage colony stimulating factor. Evidence from animal models using mice suggests that adipose tissue becomes infiltrated with macrophages, which are proportional to the total amount of fat present. These results have been followed by trials in humans that show similar results. Obesity may therefore lead to cardiovascular disease because overeating itself is pro-inflammatory and results in a chronic inflammatory immune response. Research suggests that calorie restriction causes a reduction in C-reactive protein, a marker of systemic inflammation and risk factor for cardiovascular events. This tends to suggest that calorie restriction is anti-inflammatory in nature. Models have consistently shown that calorie restriction in laboratory animals extends the life of the animals significantly and improves cardiovascular health.
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