Document Type

Article

Peer Reviewed

1

Publication Date

3-10-2017

NLM Title Abbreviation

Pharmacol Res Perspect

Journal/Book/Conference Title

Pharmacol Research & Perspectives

PubMed ID

28357127

DOI of Published Version

10.1002/prp2.301

Start Page

00301

Total Pages

13

Abstract

We recently reported that mitoquinone (mitoQ, 500 μmol/L) added to drinking water of C57BL/6J mice attenuated weight gain, decreased food intake, increased hypothalamic orexigenic gene expression, and mitigated oxidative stress when administered from the onset of high-fat (HF) feeding. Here, we examined the effects of mitoQ on pre-existing obesity in C57BL/6J mice first made obese by 107 days of HF feeding. In contrast to our preventative study, we found that already obese mice did not tolerate mitoQ at 500 μmol/L. Within 4 days of administration, obese mice markedly decreased food and water intake and lost substantial weight necessitating a dose reduction to 250 μmol/L. Food and water intake then improved. Over the next 4 weeks, body mass of the mitoQ-treated mice increased faster than vehicle-treated controls but did not catch up. Over the subsequent 10 weeks, weights of the mitoQ-treated group remained significantly less than vehicle control, but percent fat and food intake did not differ. Although the mitoQ-treated groups continued to drink less, there was no difference in percent body fluid and no laboratory evidence of dehydration at study end. At the time of killing, hypothalamic NPY gene expression was reduced in the mitoQ-treated mice . Liver fat was markedly increased by HF feeding but did not differ between mitoQ and vehicle groups and, in contrast to our previous preventative study, there was no improvement in plasma alanine amino transferase or liver hydroperoxides. In summary, administration of mitoQ to already obese mice attenuated weight gain, but showed limited overall benefit.

Keywords

OAfund, Antioxidants, coenzyme Q, leptin, mitochondria, neuropeptide Y, Obesity

Granting or Sponsoring Agency

Department of Veterans Affairs, US National Institute of Health (NIH) Grant Number: 5R01HL073166, Fraternal Order of the Eagles, NIH Predoctoral Training Program in Biotechnology Grant Number: T32 GM008365, National Institutes of Health (NIH) Grant Number: HL084207, American Heart Association (AHA) Grant Number: 14EIA18860041

Grant Number

NIH 5R01HL073166, NIH T32 GM008365, NIH HL084207, AHA 14EIA18860041

Journal Article Version

Version of Record

Published Article/Book Citation

Pharma Res Per, 5(2), 2017, e00301, http://dx.doi.org/10.1002/prp2.301

Rights

Copyright © 2017 The Author(s)

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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URL

https://ir.uiowa.edu/internalmedicine_pubs/28