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

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 high fat 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 control diet after weaning, to generate two offspring groups: C/C and HF/C. At 12 wk of age, male rats were killed and samples were collected for analysis. Maternal HF diet significantly increased plasma triacylglycerol and hepatic thiobarbituric acid reactive substance concentrations and the size of hepatic lipid droplets in offspring rats. The expression of antioxidant defense genes, such as glutathione peroxidase-1 (Gpx1), 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 p16INK4a, a marker of cellular senescence, and cyclooxygenase-2 (Cox2), a pro-inflammatory 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 (p-Rb) protein were significantly lower in HF/C offspring than in C/C offspring. The results provide the first evidence that maternal HF diet might alter antioxidant defense capacity and program the p16INK4a- dependent cellular senescence in the liver of adult offspring.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Zhang, Xiyuan

Contributors dc:contributor

• Pan, Yuan-Xiang

• Aging
• Cancer
• Oxidative stress
• Non-alcoholic fatty liver disease
• Lipid

Statement dc:rights

• Copyright 2011 Xiyuan Zhang

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/24049

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/24049