Effect of mitoquinone (Mito-Q) on neuropathic endpoints in an obese and type 2 diabetic rat model

Abstract

This study sought to determine whether the addition of mitoquinone (Mito-Q) in the diet is an effective treatment for peripheral neuropathy in animal models of diet-induced obesity (pre-diabetes) and type 2 diabetes. Unlike other anti-oxidative stress compounds investigated as a treatment for peripheral neuropathy, Mito-Q specifically targets mitochondria. Although mito-Q has been shown to reduce oxidative stress generated by mitochondria there have been no studies performed of the effect of Mito-Q on peripheral neuropathy induced by diet-induced obesity or type 2 diabetes. Diet-induced obese (12 weeks after high fat diet) or type 2 diabetic rats (12 weeks of high fat diet and 4 weeks after the onset of hyperglycemia) were treated via the diet with Mito-Q (0.93 g/kg diet) for 12 weeks. Afterwards, glucose utilization, vascular reactivity of epineurial arterioles to acetylcholine and peripheral neuropathy related endpoints were examined. The addition of Mito-Q to the diets of obese and diabetic rats improved motor and/or sensory nerve conduction velocity, cornea and intraepidermal nerve fibre density, cornea sensitivity and thermal nociception. Surprisingly, treating obese and diabetic rats with Mito-Q did not improve glucose utilization or vascular reactivity by epineurial arterioles to acetylcholine. These studies imply that mitochondrial dysfunction contributes to peripheral neuropathy in animal models of pre-diabetes and late-stage type 2 diabetes. However, improvement in peripheral neuropathy following treatment with Mito-Q was not associated with improvement in glucose utilization or vascular reactivity of epineurial arterioles to acetylcholine.

Keywords:

• Peripheral neuropathy
• diabetes
• obesity
• mitoquinone
• oxidative stress

Disclosure statement

There are no conflicts of interest to be declared by any of the authors. The content of this manuscript is new and solely the responsibility of the authors and does not necessarily represent the official views of the granting agencies.

Data availability

Since this work was done in part through support of a grant from the Veterans Affairs the original data is only available upon request. Interested parties can gain access to the data supporting conclusions of this study by contacting the senior author. Please email Dr. Mark Yorek at [email protected] or [email protected].

Additional information

Funding

This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development (RX000889-05) and by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK107339-04 and DK115256-02 from NIH.

This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development (RX000889-05) and by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK107339-04 and DK115256-02 from NIH.