TLR4 and obesity due to melanocortin 4 receptor deficiency: Given that TLR4 is highly expressed in microglia [57, 58], TLR4 signaling pathways are implicated in activated microglial phenotypes, and activated microglia are thought to drive many of the adverse effects of obesity and HFD in hippocampus and other brain regions [10, 59], TLR4 may mediate HFD-induced microglial activation and dysfunction in hippocampus.