Saturated fatty acids and inflammation: who pays the toll?

Since the discovery that obesity is associated with macrophage accumulation in adipose tissue,1,2 mechanisms by which adipose tissue becomes inflamed, resulting in insulin resistance, have remained elusive. Several studies have demonstrated that saturated fatty acids (SFAs) stimulate adipose tissue inflammation by a process that involves Toll-like receptor 4 (TLR4), a receptor that binds bacterial lipopolysaccharide (LPS). TLR4 is a pattern recognition receptor that plays a key role in the innate immune response. The observation that TLR4 deficiency protected against insulin resistance in obesity induced by a diet high in SFAs3 suggested that TLR4 was the link between diet excess and insulin resistance.3 Attenuation of diet-induced insulin resistance4,5 and adipose tissue inflammation6 also have been observed in C3H/HeJ mice with a loss of function mutation in TLR4.