Role of de novo lipogenesis in inflammation and insulin resistance in Alzheimer's disease

Abstract

Patients with Alzheimer's disease (AD) display both peripheral tissue and brain insulin resistance, the later could be a potential risk factor for cognitive dysfunction. While certain degree of inflammation is required for inducing insulin resistance, underlying mechanism(s) remains unclear. Evidence from diverse research domains suggest that elevated intracellular fatty acids of de novo pathway can induce insulin resistance even without triggering inflammation; however, the effect of saturated fatty acids (SFAs) could be detrimental due the development of proinflammatory cues. In this context, evidence suggest that while lipid/fatty acid accumulation is a characteristic feature of brain pathology in AD, dysregulated de novo lipogenesis could be a potential source for lipid/fatty acid accumulation. Therefore, therapies aimed at regulating de novo lipogenesis could be effective in improving insulin sensitivity and cognitive function in patients with AD.

Keywords: Alzheimer's disease; Cognitive dysfunction; Inflammation; Insulin resistance; de novo lipogenesis.