title: Developmental programming by high fructose decreases phosphorylation efficiency in aging offspring brain mitochondria, correlating with enhanced UCP5 expression.
abstract: Fructose has recently been observed to affect brain metabolism and cognitive function in adults. Yet, possible late-onset effects by gestational fructose exposure have not been examined. We evaluated mitochondrial function in the brain of aging (15 months) male offspring of Fischer F344 rat dams fed a high-fructose diet (50% energy from fructose) during gestation and lactation. Maternal fructose exposure caused a significantly lower body weight of the offspring throughout life after weaning, while birth weight, litter size, and body fat percentage were unaffected. Isolated brain mitochondria displayed a significantly increased state 3 respiration of 8%, with the substrate combinations malate/pyruvate, malate/pyruvate/succinate, and malate/pyruvate/succinate/rotenone, as well as a significant decrease in the P/O₂ ratio, compared with the control. Uncoupling protein 5 (UCP5) protein levels increased in the fructose group compared with the control (P=0.03) and both UCP5 mRNA and protein levels were inversely correlated with the P/O₂ ratio (P=0.008 and 0.03, respectively), suggesting that UCP5 may have a role in the observed decreased phosphorylation efficiency. In conclusion, maternal high-fructose diet during gestation and lactation has long-term effects (fetal programming) on brain mitochondrial function in aging rats, which appears to be linked to an increase in UCP5 protein levels.
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Ole H
authors.initials: OH
authors.lastname: Mortensen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Lea H
authors.initials: LH
authors.lastname: Larsen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Laura K H
authors.initials: LK
authors.lastname: Ørstrup
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Lillian H L
authors.initials: LH
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Grunnet
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Quistorff
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D004032:Diet; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000096:biosynthesis*; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; D000071245:Mitochondrial Uncoupling Proteins; D009419:Nerve Tissue Proteins; C492125:Slc25a14 protein, rat; D005632:Fructose
references.citation: J Gerontol A Biol Sci Med Sci. 2010 Aug;65(8):809-14
references.pmid: 20504892
references.citation: J Physiol. 2005 May 15;565(Pt 1):3-8
references.pmid: 15695245
references.citation: Adv Exp Med Biol. 2012;942:137-56
references.pmid: 22399421
references.citation: J Cell Mol Med. 2010 Nov;14(11):2667-74
references.pmid: 19906014
references.citation: Brain Behav. 2012 Jul;2(4):468-78
references.pmid: 22950050
references.citation: J Neurochem. 2007 Feb;100(3):650-63
references.pmid: 17263793
references.citation: Neurochem Res. 2013 Feb;38(2):282-9
references.pmid: 23266757
references.citation: J Cereb Blood Flow Metab. 1987 Dec;7(6):752-8
references.pmid: 3693430
references.citation: Eur J Appl Physiol. 2007 Dec;101(6):679-89
references.pmid: 17717681
references.citation: Nat Genet. 2003 Jul;34(3):267-73
references.pmid: 12808457
references.citation: J Physiol. 2012 May 15;590(10):2485-99
references.pmid: 22473784
references.citation: Free Radic Biol Med. 2010 Sep 15;49(6):1023-35
references.pmid: 20600837
references.citation: J Neurochem. 2001 Nov;79(3):658-68
references.pmid: 11701769
references.citation: J Nutr. 2011 Sep;141(9):1664-72
references.pmid: 21813810
references.citation: Am J Reprod Immunol. 2012 Apr;67(4):287-94
references.pmid: 22380481
references.citation: J Nutr. 2009 Jun;139(6):1228S-1235S
references.pmid: 19403716
references.citation: Br Med Bull. 2001;60:5-20
references.pmid: 11809615
references.citation: Neurobiol Aging. 2009 Apr;30(4):622-9
references.pmid: 17875347
references.citation: J Nutr Biochem. 2013 Oct;24(10):1709-16
references.pmid: 23643523
references.citation: Front Neuroendocrinol. 2013 Jan;34(1):27-46
references.pmid: 23200813
references.citation: Diabetologia. 2010 Jun;53(6):1164-73
references.pmid: 20238096
references.citation: Endocrine. 2013 Aug;44(1):79-86
references.pmid: 23065593
references.citation: Physiol Rev. 2010 Jan;90(1):23-46
references.pmid: 20086073
references.citation: Chin J Physiol. 2009 Apr 30;52(2):65-71
references.pmid: 19764341
references.citation: Ann Neurol. 2004 Apr;55(4):576-80
references.pmid: 15048898
references.citation: J Nutr Biochem. 2013 Jan;24(1):70-80
references.pmid: 22818715
references.citation: Magnes Res. 2003 Mar;16(1):7-12
references.pmid: 12735477
references.citation: ScientificWorldJournal. 2012;2012:202473
references.pmid: 23125553
references.citation: J Nutr. 1993 Dec;123(12):2158-65
references.pmid: 8263611
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
references.pmid: 11309499
references.citation: Br J Nutr. 2011 Nov;106(9):1423-32
references.pmid: 21736803
references.citation: Nutr Res. 2012 Aug;32(8):588-98
references.pmid: 22935342
references.citation: Adv Nutr. 2013 Mar 01;4(2):220-5
references.pmid: 23493538
references.citation: Hormones (Athens). 2008 Apr-Jun;7(2):101-13
references.pmid: 18477547
references.citation: J Nutr. 1991 Dec;121(12):1999-2005
references.pmid: 1941264
references.citation: Nature. 2012 Feb 01;482(7383):27-9
references.pmid: 22297952
references.citation: Nutr Rev. 2007 Jun;65(6 Pt 2):S13-23
references.pmid: 17605309
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713