title: A maternal high-fat diet represses the expression of antioxidant defense genes and induces the cellular senescence pathway in the liver of male offspring rats.
abstract: Maternal high-fat (HF) diet feeding is associated with increased risk of developing metabolism-related diseases in adult offspring, including chronic liver disease. The present study tested the hypothesis that maternal HF diet leads to a decreased antioxidant defense capacity and causes cellular senescence in liver of adult offspring rats, which might increase risk of developing chronic liver disease. Timed-pregnant Sprague Dawley rats were fed a HF diet (45% of energy from fat) or a control (C) diet (16% of energy from fat) during gestation and lactation. The resulting offspring were fed a C diet after weaning to generate 2 offspring groups: C diet-fed offspring of dams fed C diet (C/C) and C diet-fed offspring of dams fed a HF diet (HF/C). At 12 wk of age, male rats were killed and samples were collected for analysis. Maternal HF diet significantly increased plasma TG and hepatic TBARS concentrations and the size of hepatic lipid droplets in offspring rats. The expression of antioxidant defense genes, such as glutathione peroxidase-1, Cu/Zn superoxide dismutase (Sod1), paraoxonase enzymes (Pon1, Pon2, and Pon3), were significantly lower in the liver of HF/C pups than in C/C pups. The expression of Inhibitor of cyclin dependent Kinase 4a (p16INK4a), a marker of cellular senescence, and cyclooxygenase-2 (Cox2), a proinflammatory marker, was significantly higher in the HF/C offspring group than in the C/C offspring group. Western-blot analysis shows that cyclin D1 and phosphorylated retinoblastoma protein were significantly lower in HF/C offspring than in C/C offspring. The results provide the first evidence to our knowledge that maternal HF diet might alter antioxidant defense capacity and program the p16INK4a-dependent cellular senescence in the liver of adult offspring.
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Xiyuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Rita
authors.initials: R
authors.lastname: Strakovsky
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Pan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D043303:Aryldialkylphosphatase / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics* / Q000502:physiology; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D015870:Gene Expression; D019942:Genes, p16; D005979:Glutathione Peroxidase / Q000235:genetics; D008099:Liver / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D004041:Dietary Fats; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D043303:Aryldialkylphosphatase; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat