title: Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth.
abstract: BACKGROUND
  It is well established that low birth weight and accelerated postnatal growth increase the risk of liver dysfunction in later life. However, molecular mechanisms underlying such developmental programming are not well characterized, and potential intervention strategies are poorly defined.
  
  
  OBJECTIVE
  We tested the hypotheses that poor maternal nutrition and accelerated postnatal growth would lead to increased hepatic fibrosis (a pathological marker of liver dysfunction) and that postnatal supplementation with the antioxidant coenzyme Q10 (CoQ10) would prevent this programmed phenotype.
  
  
  METHODS
  A rat model of maternal protein restriction was used to generate low-birth-weight offspring that underwent accelerated postnatal growth (termed "recuperated"). These were compared with control rats. Offspring were weaned onto standard feed pellets with or without dietary CoQ10 (1 mg/kg body weight per day) supplementation. At 12 mo, hepatic fibrosis, indexes of inflammation, oxidative stress, and insulin signaling were measured by histology, Western blot, ELISA, and reverse transcriptase-polymerase chain reaction.
  
  
  RESULTS
  Hepatic collagen deposition (diameter of deposit) was greater in recuperated offspring (mean ± SEM: 12 ± 2 μm) than in controls (5 ± 0.5 μm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor α: 64% ± 24% increase; P < 0.05), lipid peroxidation (4-hydroxynonenal, measured by ELISA: 0.30 ± 0.02 compared with 0.19 ± 0.05 μg/mL per μg protein; P < 0.05), and hyperinsulinemia (P < 0.05). CoQ10 supplementation increased (P < 0.01) hepatic CoQ10 concentrations and ameliorated liver fibrosis (P < 0.001), inflammation (P < 0.001), some measures of oxidative stress (P < 0.001), and hyperinsulinemia (P < 0.01).
  
  
  CONCLUSIONS
  Suboptimal in utero nutrition combined with accelerated postnatal catch-up growth caused more hepatic fibrosis in adulthood, which was associated with higher indexes of oxidative stress and inflammation and hyperinsulinemia. CoQ10 supplementation prevented liver fibrosis accompanied by downregulation of oxidative stress, inflammation, and hyperinsulinemia.
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and janeadkins@googlemail.com.
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors.forename: Denise S
authors.initials: DS
authors.lastname: Fernandez-Twinn
authors.affiliation: Neurometabolic Unit, National Hospital, University College London, London, United Kingdom.
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.affiliation: Neurometabolic Unit, National Hospital, University College London, London, United Kingdom.
authors.forename: Viruna
authors.initials: V
authors.lastname: Neergheen
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Aiken
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors.forename: Malgorzata S
authors.initials: MS
authors.lastname: Martin-Gronert
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors.forename: Josie M
authors.initials: JM
authors.lastname: McConnell
authors.affiliation: University of Cambridge Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom; and.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism; D018753:Diet, Protein-Restricted / Q000009:adverse effects; D019587:Dietary Supplements; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000178:diet therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006946:Hyperinsulinism / Q000209:etiology / Q000517:prevention & control; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D044342:Malnutrition / Q000503:physiopathology; D039382:Maternal Nutritional Physiological Phenomena; D018384:Oxidative Stress; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014886:Weaning
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D014451:Ubiquinone; C024989:coenzyme Q10
keywords: accelerated postnatal growth; coenzyme Q; developmental programming; liver disease; low birth weight