Adipokines, systemic inflammation and inflamed adipose tissue in obesity and insulin resistance

Abstract

Obesity and its complications are characterized by elevated circulating levels of inflammation markers like CRP, IL-6 and serum amyloid A.

Although several cells secrete these markers, the adipose tissue seems to play a pivotal role for the proinflammatory state. Obesity with enlarged adipose cells leads to a marked increase in the expression of pro-inflammatory cytokines in the adipose tissue while expression of the anti-inflammatory adipokine, adiponectin, is reduced. The mechanisms for this are currently unknown but a consequence is the recruitment of inflammatory cells into the adipose tissue which, thus, becomes inflamed. Animal experiments have shown that this is associated with a clear accentuation of degree of insulin resistance.

Invasion of inflammatory cells leads to the release of TNFa, which normally is not secreted by the adipose cells. The increased levels of cytokines in the adipose tissue have marked consequences for the normal differentiation of the preadipocytes. These cells become proinflammatory and the normal phenotype, i.e., lipid-accumulating and insulin-sensitive cells, is suppressed.

Although inflammation in the adipose tissue also leads to a reduced insulin sensitivity, recent data have shown that induction of insulin resistance by itself in the adipose tissue also is proinflammatory since insulin can exert an anti-inflammatory effect through its cross-talk with the IL-6 signaling cascade.