Detrimental impact of hyperlipidemia on the peripheral nervous system: A novel target of medical epidemiological and fundamental research study

Abstract

Recently, epidemiological studies on the etiology of peripheral neuropathies have revealed that hyperlipidemia is a novel risk factor. Plasma lipid levels were confirmed to be associated with the incidence of many peripheral neuropathies including axonal distal polyneuropathy, vision and hearing loss, motor nerve system lesions and sympathetic nerve system dysfunction. Moreover, different lipid components such as cholesterol, triacylglycerols and lipoprotein are involved in the pathogenesis of these neuropathies. This review aimed to discuss the effect of hyperlipidemia on the peripheral nervous system and its association with peripheral neuropathies. Furthermore, a detailed discussion focusing on the explicit mechanisms related to hyperlipidemia-induced peripheral neuropathies is presented here. These mechanisms, including intracellular oxidative stress, inflammatory lesions, ischemia and dysregulation of local lipid metabolism, share pathways and interact mutually. In addition, we examined current information on clinical trials to prevent and treat peripheral neuropathies caused by hyperlipidemia, with a predictive discussion regarding the orientation of future investigations.

Keywords: hyperlipidemia; neuropathy; peripheral nervous system; reviews.

Figure 1

Effect of oxidized low-density lipoproteins (oxLDLs) binding to lectin-like oxLDL receptor-1 (LOX-1). LOX-1 on dorsal root ganglia (DRG) neurons binds to oxLDLs. OxLDLs may be endocytosed or transcytosed. Receptor binding initiates a signaling pathway leading to the activation of NAD(P)H oxidase and may also alter mitochondrial generation of reactive oxygen species (ROS). Glucose independently affects these same cellular targets[32]. NADPH: nicotinamide adenine dinucleotide phosphate hydratenucleotide; NADP⁺: oxidated NADPH; NOX: nitrogen oxides; pphox complex: phagocytic oxidase complex; TCA: tricarboxylicacidcycle.