Dyslipidemia-Induced Neuropathy in Mice: the Role of oxLDL/LOX-1
Authors Andrea M. Vincent, John M. Hayes, Lisa L. McLean, Anuradha Vivekanandan-Giri,
Subramaniam Pennathur, and Eva L. Feldman
Submitted By Eva Feldman on 1/12/2009
Status Published
Journal Diabetes
Year 2009
Date Published 10/1/2009
Volume : Pages 58(10) : 2376 - 2385
PubMed Reference 19592619
Abstract Objective: Neuropathy is a frequent and severe complication of diabetes.
Multiple metabolic defects in type 2 diabetic patients result in oxidative
injury of dorsal root ganglia (DRG) neurons. Our previous work focused on
hyperglycemia clearly demonstrates induction of mitochondrial oxidative stress
and acute injury in DRG neurons; however, this mechanism is not the only factor
that produces neuropathy in vivo. Dyslipidemia also correlates with the
development of neuropathy, even in pre-diabetic patients. This study was
designed to explore the contribution of dyslipidemia in neuropathy. Research
Design and Methods: Mice (n=10) were fed a control (10%kcal%fat) or high fat
(45%kcal%fat) diet to explore the impact of plasma lipids on the development of
neuropathy. We also examined oxidized lipid-mediated injury in cultured DRG
neurons from adult rat using oxidized low density lipoproteins (oxLDL). Results:
Mice on a high fat diet have increased oxLDL and systemic and nerve oxidative
stress. They develop nerve conduction velocity (NCV) and sensory deficits prior
to impaired glucose tolerance. In vitro, oxLDL lead to severe DRG neuron
oxidative stress via interaction with the receptor LOX-1 and subsequent NAD(P)H
oxidase activity. Oxidative stress resulting from oxLDL and high glucose is
additive. Conclusions: Multiple metabolic defects in type 2 diabetes directly
injure DRG neurons through different mechanisms that all result in oxidative
stress. Dyslipidemia leads to high levels of oxLDL that injure DRG neurons via
LOX-1 and contribute to the development of diabetic neuropathy.

Investigators with authorship
Eva FeldmanUniversity of Michigan


Olr1oxidized low density lipoprotein (lectin-like) receptor 1