Saturated Fatty Acid and TLR Signaling Link β Cell Dysfunction and Islet Inflammation

Consumption of foods high in saturated fatty acids (FAs) as well as elevated levels of circulating free FAs are known to be associated with T2D. Though previous studies showed inflammation is crucially involved in the development of insulin resistance, how inflammation contributes to beta cell dysfunction has remained unclear. We report here the saturated FA palmitate induces beta cell dysfunction in vivo by activating inflammatory processes within islets. Through a combination of in vivo and in vitro studies, we show beta cells respond to palmitate via the TLR4/MyD88 pathway and produce chemokines that recruit CD11b(+)Ly-6C(+) M1-type proinflammatory monocytes/macrophages to the islets. Depletion of M1-type cells protected mice from palmitate-induced beta cell dysfunction. Islet inflammation also plays an essential role in beta cell dysfunction in T2D mouse models. Collectively, these results demonstrate a clear mechanistic link between beta cell dysfunction and inflammation mediated at least in part via the FFA-TLR4/MyD88 pathway.