Silicon-enriched meat consumption mitigates brain cortex damage associated with diabetic dyslipidemia in a late-stage type 2 diabetes mellitus rat model

Neuroprotective properties of silicon have been reported, particularly in mitigating dementia and Alzheimer's disease due to its ability to reduce aluminum bioavailability. However, its potential as a nutritional adjuvant in reducing brain damage associated with hypercholesterolemia and central insulin resistance (IR) in late-stage type 2 diabetes mellitus (T2DM) remains unexplored. This study aimed to evaluate the effects of silicon-enriched meat (Si-RM) on the brain cortex of T2DM rats. Rat models of early-stage-T2DM (ED) (n = 8) and late-stage-T2DM (LD) (n = 16) were induced by high-saturated fat diet and high-saturated fat high-cholesterol diet plus streptozotocin/nicotinamide injection, respectively. A control meat (C-RM) was included in the diet of both ED and LD groups. Finally, after confirming hyperglycemia in LD rats, the C-RM was replaced by Si-RM in half of the animals for the last five weeks of the study, obtaining the LD-Si group (n = 8), while the other half continued eating C-RM. In LD rats pathological outcomes included: harmful oxysterol profile, decreased antioxidant defenses, neuroinflammation, brain IR, augmented glucose uptake and impaired cholinergic transmission. Si-RM consumption ameliorates these key outcomes by reducing brain levels of pro-oxidant oxysterols (25-OHC and 27-OHC) to levels of ED rats. Antioxidant defenses, including SOD and arylesterase activity, were enhanced, and inflammatory markers, such as GFAP, IL6, and TNFα, were reduced compared to LD and ED counterparts. Notably, silicon restored brain insulin signaling, normalized glucose uptake via GLUT3, and shifted to an acetylcholine-preserving profile, significantly mitigating neurodegenerative risks. This study demonstrates for the first time that silicon, provided as a functional dietary ingredient of meat-products, exhibited a capacity to partially counteract brain cortex metabolic damage caused by T2DM.