High-Fat Diet Induces Hepatic Insulin Resistance and Impairment of Synaptic Plasticity

摘要: High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted 3 month-old C57BL/6J mice fed either a normal chow (control group) or HFD (60% calorie from fat; for 12 weeks. This was characterized as function time in terms body weight, fasting blood glucose levels, HOMA-IR values, plasma triglycerides. IRS-1/Akt pathway assessed primary hepatocytes homogenates. effect by electrophysiology, input/output responses long-term potentiation. HFD-fed exhibited significant increase higher glucose- levels plasma, lower tolerance, values. In liver, elicited (a) decrease receptor substrate (IRS-1) phosphorylation on Tyr608 Ser307 phosphorylation, indicative IRS-1 inactivation; (b) these changes were accompanied inflammatory increases the expression NFκB iNOS activation MAP kinases p38 JNK; (c) showed decreased cellular oxygen consumption rates (indicative mitochondrial functional impairment); this can be ascribed partly to PGC1α biogenesis. brain, feeding an inactivation and, consequentially, membrane localization transporters GLUT3/GLUT4; suppression ERK/CREB pathway, (d) substantial potentiation CA1 region hippocampus impaired plasticity). It surmised that weeks induce systemic resistance impacts profoundly activity, i.e., plasticity.