title: A mitochondrial-targeted coenzyme q analog prevents weight gain and ameliorates hepatic dysfunction in high-fat-fed mice.
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.
authors.affiliation: 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.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Fink
authors.affiliation: 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.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Herlein
authors.affiliation: 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.
authors.forename: Deng Fu
authors.initials: DF
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Kulkarni
authors.affiliation: 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.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Weidemann
authors.affiliation: 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.
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Grobe
authors.affiliation: 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.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
authors.affiliation: 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.
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 (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.
authors.forename: William I
authors.initials: WI
authors.lastname: Sivitz
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D008107:Liver Diseases / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015430:Weight Gain / Q000187:drug effects* / Q000502:physiology
chemical_list: D004041:Dietary Fats; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone