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

Xiyuan Zhang, Rita Strakovsky, Dan Zhou, Yukun Zhang, Yuan Xiang Pan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1254-1259
Number of pages6
JournalJournal of Nutrition
Volume141
Issue number7
DOIs
StatePublished - Jul 1 2011

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this