INSR and Insulin resistance: Excessive fat intake leads to the accumulation of free fatty acids, malonyl-CoA, and diacylglycerol (DAG) in tissues, which activates protein kinase C (PKC), and this activation inhibits AMPK by phosphorylating serine residues at positions 485/491 and also impairs insulin signaling by inhibiting insulin receptor substrates, contributing to insulin resistance (Coughlan et al., 2013).