Neuropathy and the metabolic syndrome

Abstract

Obesity and the metabolic syndrome (MetS) are major global health challenges that contribute significantly to the rising prevalence of type 2 diabetes (T2D) and neuropathy. Neuropathy, a common and disabling complication of T2D, is characterized by progressive distal-to-proximal axonal degeneration, driven in part by mitochondrial dysfunction in both neurons and axons. Recent evidence points to the toxic effects of saturated fatty acids on peripheral nerve health, with studies demonstrating that these fats impair mitochondrial function and bioenergetics, leading to distal axonal loss. Conversely, monounsaturated fatty acids are found to be neuroprotective, restoring mitochondrial function and preventing neuropathy. These findings suggest that dietary factors play a crucial role in the pathogenesis of neuropathy associated with metabolic dysregulation and emphasize the need for lifestyle interventions and therapies that target these newly identified mechanisms.

Keywords: Diabetes; Dyslipidemia; Metabolic syndrome; Neuropathy; Obesity; Prediabetes.

Fig. 1

Nerve and metabolic health. Diets rich in fruits, vegetables, and health fats, particularly monounsaturated fatty acids (MUFAs), along with exercise, support normal mitochondrial (mito) ATP production, energetics, and trafficking, which in turn promote healthy nerve function. In contrast, excess saturated fatty acids (SFAs) from a Westernized diet compromise mito function, leading to impaired mito trafficking, distal energetic failure, and peripheral nerve degeneration. ATP, adenosine triphosphate; MetS, metabolic syndrome; ROS, reactive oxygen species; T2D, type 2 diabetes. Image was created using BioRender.com.