The underlying etiology of metabolic syndrome is extra weight, obesity, lack of physical activity, and genetic predisposition. The crux of the syndrome is a buildup of adipose tissue and tissue dysfunction that in turn leads to insulin resistance. Proinflammatory cytokines such as tumor necrosis factor, leptin, adiponectin, plasminogen activator inhibitor, and resistin, are released from the enlarged adipose tissue, which alters and impacts insulin handling adversely. Insulin resistance can be acquired or may be due to genetic disposition. Impairment of the signaling pathway, insulin receptor defects, and defective insulin secretion can all contribute towards insulin resistance. Over time, the culmination of this cause development of metabolic syndrome that presents as vascular and autonomic damage.
The distribution of body fat is also important, and it is known that upper body fat plays a strong role in developing insulin resistance. Fat accumulation can be intraperitoneal (visceral fat) or subcutaneous. Visceral fat may contribute to insulin resistance more strongly than subcutaneous fat. However, both are known to play a role in the development of the metabolic syndrome. In upper body obesity, high levels of nonesterified fatty acids are released from the adipose tissue causing lipid to accumulate in other parts of the body such as liver and muscle, further perpetuating insulin resistance.