Journal article
A mitochondrial-targeted coenzyme q analog prevents weight gain and ameliorates hepatic dysfunction in high-fat-fed mice
The Journal of pharmacology and experimental therapeutics, Vol.351(3), pp.699-708
12/2014
DOI: 10.1124/jpet.114.219329
PMCID: PMC4244581
PMID: 25301169
Abstract
We hypothesized that the mitochondrial-targeted antioxidant, mitoquinone (mitoQ), known to have mitochondrial uncoupling properties, might prevent the development of obesity and mitigate liver dysfunction by increasing energy expenditure, as opposed to reducing energy intake. We administered mitoQ or vehicle (ethanol) to obesity-prone C57BL/6 mice fed high-fat (HF) or normal-fat (NF) diets. MitoQ (500 µM) or vehicle (ethanol) was added to the drinking water for 28 weeks. MitoQ significantly reduced total body mass and fat mass in the HF-fed mice but had no effect on these parameters in NF mice. Food intake was reduced by mitoQ in the HF-fed but not in the NF-fed mice. Average daily water intake was reduced by mitoQ in both the NF- and HF-fed mice. Hypothalamic expression of neuropeptide Y, agouti-related peptide, and the long form of the leptin receptor were reduced in the HF but not in the NF mice. Hepatic total fat and triglyceride content did not differ between the mitoQ-treated and control HF-fed mice. However, mitoQ markedly reduced hepatic lipid hydroperoxides and reduced circulating alanine aminotransferase, a marker of liver function. MitoQ did not alter whole-body oxygen consumption or liver mitochondrial oxygen utilization, membrane potential, ATP production, or production of reactive oxygen species. In summary, mitoQ added to drinking water mitigated the development of obesity. Contrary to our hypothesis, the mechanism involved decreased energy intake likely mediated at the hypothalamic level. MitoQ also ameliorated HF-induced liver dysfunction by virtue of its antioxidant properties without altering liver fat or mitochondrial bioenergetics.
Details
- Title: Subtitle
- A mitochondrial-targeted coenzyme q analog prevents weight gain and ameliorates hepatic dysfunction in high-fat-fed mice
- Creators
- Brian D Fink - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaJudith A Herlein - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaDeng Fu Guo - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaChaitanya Kulkarni - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaBenjamin J Weidemann - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaLiping Yu - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaJustin L Grobe - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaKamal Rahmouni - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaRobert J Kerns - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, IowaWilliam I Sivitz - Department of Internal Medicine/Endocrinology, University of Iowa and the Iowa City Veterans Affairs Medical Center (B.D.F., J.A.H., W.I.S.), and the Departments of Pharmacology (D.F.G., B.J.W., J.L.G.), Pharmaceutical Sciences and Experimental Therapeutics (C.K., R.J.K.), Biochemistry (L.Y.), Pharmacology and Internal Medicine/Cardiology (K.R.), and Primary Laboratory (W.I.S.), University of Iowa, Iowa City, Iowa william-sivitz@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of pharmacology and experimental therapeutics, Vol.351(3), pp.699-708
- DOI
- 10.1124/jpet.114.219329
- PMID
- 25301169
- PMCID
- PMC4244581
- NLM abbreviation
- J Pharmacol Exp Ther
- ISSN
- 0022-3565
- eISSN
- 1521-0103
- Publisher
- United States
- Copyright
- This article has been contributed to by US Government employees and their work is in the public domain in the USA This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Grant note
- R01 HL073166 / NHLBI NIH HHS I01 BX000285 / BLRD VA P01 HL084207 / NHLBI NIH HHS 5R01-HL073166 / NHLBI NIH HHS T32-GM008365 / NIGMS NIH HHS T32 GM008365 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Neuroscience and Pharmacology; Biochemistry and Molecular Biology; Medicine Administration; Endocrinology and Metabolism; Medicinal and Natural Products Chemistry; Internal Medicine
- Record Identifier
- 9984040272802771
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