title: Metabolic effects of a mitochondrial-targeted coenzyme Q analog in high fat fed obese mice.
abstract: We recently reported that mitoquinone (mitoQ, 500μmol/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 500μmol/L. Within 4 days of administration, obese mice markedly decreased food and water intake and lost substantial weight necessitating a dose reduction to 250μmol/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.
authors.affiliation: Department of Internal Medicine/Endocrinology University of Iowa and the Iowa City Veterans Affairs Medical Center Iowa City Iowa 52242.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Fink
authors.affiliation: Department of Pharmacology University of Iowa Iowa City Iowa 52242.
authors.forename: Deng Fu
authors.initials: DF
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics University of Iowa Iowa City Iowa 52242.
authors.forename: Chaitanya A
authors.initials: CA
authors.lastname: Kulkarni
authors.affiliation: Departments of Pharmacology and Internal Medicine University of Iowa Iowa City Iowa 52242.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.affiliation: Department of Pharmaceutical Sciences and Experimental Therapeutics University of Iowa Iowa City Iowa 52242.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kerns
authors.affiliation: Department of Internal Medicine/Endocrinology University of Iowa and the Iowa City Veterans Affairs Medical Center Iowa City Iowa 52242.
authors.forename: William I
authors.identifier: 0000-0002-7829-0189
authors.initials: WI
authors.lastname: Sivitz
keywords: Antioxidants; Obesity; coenzyme Q; leptin; mitochondria; neuropeptide Y