Research article summary (published 8 Jul 2009):

Dyslipidemia-induced neuropathy in mice: the role of oxLDL/LOX-1.

Full 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 LDLs (oxLDLs). RESULTS: Mice on a high-fat diet have increased oxLDLs and systemic and nerve oxidative stress. They develop nerve conduction velocity (NCV) and sensory deficits prior to impaired glucose tolerance. In vitro, oxLDLs lead to severe DRG neuron oxidative stress via interaction with the receptor lectin-like oxLDL receptor (LOX)-1 and subsequent NAD(P)H oxidase activity. Oxidative stress resulting from oxLDLs 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 oxLDLs that may injure DRG neurons via LOX-1 and contribute to the development of diabetic neuropathy.

Author information

Author/s: Vincent, Andrea M (AM); Hayes, John M (JM); McLean, Lisa L (LL); Vivekanandan-Giri, Anuradha (A); Pennathur, Subramaniam (S); Feldman, Eva L (EL);

Affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA. andreav(-atsign-)umich.edu

Grants: R24DK082841 (Agency:NIDDK NIH HHS) ; U01 DK076160 (Agency:NIDDK NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Diabetes (Diabetes), published in United States. (Language: eng)

Reference: 2009-Oct; vol 58 (issue 10) : pp 2376-85

Dates: Created 2009/10/01; Completed 2009/10/23;

PMID: 19592619, status: MEDLINE (last retrieval date: 10/23/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Blood Glucose - metabolism DNA Fragmentation Diabetes Mellitus, Type 2 - complications Diabetic Neuropathies - blood; etiology; physiopathology Dietary Fats - adverse effects Dyslipidemias - complications Female Ganglia, Spinal - cytology; physiopathology Glucose Tolerance Test Hindlimb - physiopathology Insulin - blood

Insulin - blood Lipids - blood Lipoproteins, LDL - adverse effects; metabolism Mice Mice, Inbred C57BL Nerve Fibers - pathology Neural Conduction - physiology Neurons - cytology; physiology Rats Rats, Sprague-Dawley Reactive Oxygen Species - metabolism Scavenger Receptors, Class E - metabolism

Associated Chemicals: Blood Glucose (0) ; Dietary Fats (0) ; Lipids (0) ; Lipoproteins, LDL (0) ; Olr1 protein, mouse (0) ; Reactive Oxygen Species (0) ; Scavenger Receptors, Class E (0) ; oxidized low density lipoprotein (0) ; Insulin (11061-68-0)

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