Coenzyme Q10 prevents hepatic fibrosis, inflammation, and oxidative stress in a male rat model of poor maternal nutrition and accelerated postnatal growth.

Autor:	Tarry-Adkins, Jane L., Fernandez-Twinn, Denise S., Hargreaves, Iain P., Neergheen, Viruna, Aiken, Catherine E., Martin-Gronert, Malgorzata S., McConnell, Josie M., Ozanne, Susan E.
Předmět:	BLOOD sugar analysis LIVER disease prevention FIBROSIS ANALYSIS of variance ANIMAL experimentation ANTHROPOMETRY COLLAGEN DIETARY supplements ENZYME-linked immunosorbent assay HISTOLOGICAL techniques HUMAN growth HYPERINSULINISM INFLAMMATION INSULIN INTERLEUKINS LIVER LONGITUDINAL method MALNUTRITION in pregnancy LIPID peroxidation (Biology) POLYMERASE chain reaction PROBABILITY theory RATS RESEARCH funding STAINS & staining (Microscopy) STATISTICS TUMOR necrosis factors UBIQUINONES WESTERN immunoblotting DATA analysis OXIDATIVE stress REVERSE transcriptase polymerase chain reaction DATA analysis software DESCRIPTIVE statistics IN vivo studies METABOLISM PREVENTION
Zdroj:	American Journal of Clinical Nutrition; 2/1/2016, Vol. 103 Issue 2, p579-588, 10p, 3 Charts, 5 Graphs
Abstrakt:	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. Objectives: 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. Design: 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 mm) (P < 0.001). This was associated with greater inflammation (interleukin 6: 38% ± 24% increase; P < 0.05; tumor necrosis factor a: 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 mg 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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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