Relationship Between Brain Insulin Resistance, Carbohydrate Consumption, and Protein Carbonyls, and the Link Between Peripheral Insulin Resistance, Fat Consumption, and Malondialdehyde

The consumption of a high-fat (HFD) or high-carbohydrate/low-fat (LFD) diet is related to insulin resistance; however, central and peripheral alterations can occur independently. In this study, the timeline of insulin resistance was determined while taking into consideration the role of diet in oxidative damage. Background/Objectives: The aim of this study was to ascertain whether a HFD or LFD induces peripheral insulin resistance (PIR) before brain insulin resistance (BIR), and whether the timing of these alterations correlates with heightened oxidative damage markers in plasma, adipose tissue, and the cerebral cortex. Methodology and Results: Three-month-old C57BL/6 male mice were fed with a HFD, LFD, or standard diet for 1, 2, or 3 months. Glucose and insulin tolerance tests were performed to determine PIR, and the hypothalamic thermogenic response to insulin was used to determine their BIR status. For oxidative damage, the levels of malondialdehyde (MDA) and the protein carbonyl group (PCO) and the enzymatic activity of glutathione peroxidase (GSH-Px) were evaluated in plasma, white adipose tissue, brown adipose tissue, and the cerebral cortex. PIR occurred at 3 months of the HFD, but MDA levels in the white adipose tissue increased at 2 months. BIR occurred at 1 and 2 months of the LFD, but the enzymatic activity of GSH-Px was lower at 1 month and the amount of the PCO increased at 2 months. Conclusions: The intake of a HFD or LFD of different durations can influence the establishment of PIR or BIR, and oxidative damage in the fat tissue and cerebral cortex can play an important role.