Maternal antioxidant supplementation prevents adiposity in the offspring of Western diet-fed rats

Abstract

Objective: Obesity in pregnancy significantly increases the risk of the offspring developing obesity after birth. The aims of this study were to test the hypothesis that maternal obesity increases oxidative stress during fetal development, and to determine whether administration of an antioxidant supplement to pregnant Western diet-fed rats would prevent the development of adiposity in the offspring.

Research design and methods: Female Sprague Dawley rats were started on the designated diet at 4 weeks of age. Four groups of animals were studied: control chow (control); control + antioxidants (control+Aox); Western diet (Western); and Western diet + antioxidants (Western+Aox). The rats were mated at 12 to 14 weeks of age, and all pups were weaned onto control diet.

Results: Offspring from dams fed the Western diet had significantly increased adiposity as early as 2 weeks of age as well as impaired glucose tolerance compared with offspring of dams fed a control diet. Inflammation and oxidative stress were increased in preimplantation embryos, fetuses, and newborns of Western diet-fed rats. Gene expression of proadipogenic and lipogenic genes was altered in fat tissue of rats at 2 weeks and 2 months of age. The addition of an antioxidant supplement decreased adiposity and normalized glucose tolerance. CONCLUSIONS; Inflammation and oxidative stress appear to play a key role in the development of increased adiposity in the offspring of Western diet-fed pregnant dams. Restoration of the antioxidant balance during pregnancy in the Western diet-fed dam is associated with decreased adiposity in offspring.

FIG. 1.

Weights of female dams in the four study groups. Animals were started on the diets at weaning at 4 weeks of age. The negative numbers refer to weeks before pregnancy, 0 is at breeding, and the positive numbers refer to weeks during pregnancy; n = 10 dams in each group. *P < 0.05 Western and Western+Aox versus control diet.

FIG. 2.

A: Maternal antioxidant supplement normalizes body fat in 2-week-old offspring of Western diet-fed rats. At 2 weeks of age, total and visceral fat were measured by Dexa scanning. White bar represents total fat and black bar represents visceral fat. Data shown are ratio of fat mass and body weight (percentage of total and visceral fat ± SEM), n = 5 animals in each group; *P < 0.05 Western diet versus control, control+Aox, and Western+Aox; **P < 0.05 Western+Aox versus Western diet. B: Maternal antioxidant supplement normalizes body fat in 2 month-old offspring of Western diet-fed rats. At 2 months of age, total and visceral fat were measured by Dexa scanning. White bar represents total fat and black bar represents visceral fat. Data shown are percentages of total and visceral fat ± SEM; n = 5 animals each group, *P < 0.05 Western diet versus Control, Control+Aox, and Western+Aox; **P < 0.05 versus Western+Aox versus Western diet.

FIG. 3.

Maternal antioxidant supplement improves glucose tolerance in 2-month-old offspring of Western diet-fed rats. At 2 months of age, offspring were given 2 g glucose/kg intraperitoneally and glucose was measured 15, 30, 60, and 120 min after injection. Data shown are ± SEM; n = 5 for each group; *P < 0.05 Western diet versus control, control+Aox, and Western+Aox.

FIG. 4.

Altered redox state in preimplantation embryos of Western diet-fed rats. Preimplantation embryos were harvested from pregnant rats, and GSH (A), GSSG (B), and ROS (C) levels were measured as described in methods. Data shown are ± SEM, n = 3 litters for each group, *P < 0.05 Western diet versus control, Aox+control, and Western+Aox; **P < 0.05 versus Western+Aox versus Western diet.

FIG. 5.

Maternal antioxidant supplement decreases inflammation and oxidative stress in fetal and neonatal offspring of obese dams. Serum was obtained from day 18 gestation fetuses and day 1 newborns and CRP (A), TBARS (B), and GSH/GSSG (C) were measured. Data shown are ± SEM; n = 4 litters for each group; *P < 0.05 Western diet versus control, control+Aox, and Western+Aox; **P < 0.05 versus Western+Aox versus Western diet.

FIG. 6.

Maternal antioxidant supplement normalizes gene expression in fat tissue from offspring of obese dams. Visceral fat tissue was harvested from 2-week-old (A) and 2-month-old (B) offspring and mRNA isolated as described in methods. Data shown are ± SEM; n = 4 litters for each group; *P < 0.05 Western diet versus control, control+Aox, and Western+Aox; **P < 0.05 versus Western+Aox versus Western diet.