Postnatally induced metabolic and oxidative changes associated with maternal high-fat consumption were mildly affected by Quercetin-3-O-rutinoside treatment in rats

Abstract

Oxidative stress is usually associated with prolonged intake of high-fat diet (HFD). However, little is known about the impact of maternal HFD on endogenous modulation of antioxidant-defence-enzyme-network, its link to adverse fetal growth and overall effects of Quercetin-3-o-rutinoside (QR) supplementation. Sprague-Dawley rats were initially assigned to normal diet (ND) or HFD for 8 weeks and mated. Post-conception, rats were further divided into four groups, of which two groups had diets supplemented with QR while others continued with their respective diets until delivery. Measurements include food and water consumption, physical parameters (body weight, body mass index (BMI) and fur appearance), oral glucose tolerance, lipid profiles, and placental/liver oxidative changes. We observed that water consumption was significantly increased in dams fed HFD without marked differences in food intake, body weight, BMI and glucose tolerance. Surprisingly, offspring of HFD-fed dams had reduced body weight marked by delayed fur appearance compared to the ND offspring. In dams, there were alterations in lipid profile. Lipid peroxidation was increased in the placenta and liver of gestational day (GD) 19 HFD-fed dams and their postnatal day (PND) 21 male offspring. There was evidence of HFD-induced nitrosative stress in dams and PND28 female offspring. Adaptive defence indicate decreased placenta and liver superoxide dismutase (SOD) levels as well as differential changes in total antioxidant capacity (TAC) and catalase (CAT) activity in HFD treated dams and their progenies. Overall, the results indicate that intrauterine metabolic alterations associated with maternal high-fat consumption may induce oxidative challenge in the offspring accompanied by mild developmental consequences, while QR supplementation has little or no beneficial effects.

Keywords: Developmental alterations; High-fat diet; Intrauterine; Metabolic changes; Oxidative stress; Quercetin-3-O-rutinoside.

Figure 1

Schematic showing experimental design and timeline of the study. Female SD rats were randomly assigned to dietary treatment groups, ND-fed or HFD-fed groups (n = 28/group) for approximately 8 weeks. Thereafter, these groups of rats were mated with their male counterparts who received normal rat chow and regrouped after conception, based on the dietary treatments supplemented with or without QR. It is worth noting that dietary treatments continued throughout gestation. Half set of the pregnant rats (n = 7/group) were killed at GD19, their placenta and liver were harvested. The remaining pregnant rats were allowed to litter naturally and hereafter referred to as PP21 dams. Both PP21 dams and one-third of their progenies were killed at PND21 after weaning. The remaining two-third of the offspring were killed at PND 28 and 35. At all the killing time-points, liver was removed and preserved for subsequent biochemical analyses.

Figure 2

Indicate food intake (a) and total water consumed (b) by dams during 8 weeks of HFD exposure. Also, body weight (d) and BMI (c) of dams, and differences in body weight of male (e) and female (f) offspring rats were measured at PND 21, 28 and 35. Differences in fur appearance of offspring of control dams (ND or ND/QR; gi) and HFD-fed dams (HFD or HFD/QR; gii) observed at PND 28. Data shown represents mean ± SEM; dams, n = 6 or 7 per group; offspring, n = 6 per group. ∗P < 0.05, ND vs. HFD, HFD/QR; ^ɸP < 0.05, HFD vs. ND/QR; ^‡P < 0.05, ND/QR vs. HFD/QR; Student's t-test; Two-way ANOVA, followed by Bonferroni post hoc comparison test. Arrows indicate regions of late fur appearance.

Figure 3

OGTT and lipogram results obtained from dams after 8 weeks of HFD consumption. Fasting blood glucose (a), TC (b), triglycerides (c), HDL (d) and LDL (e) levels in dam's blood post high fat meal. Data shown represents mean ± SEM; OGTT, n = 10 per group; Lipids, n = 4 per group (please note that results from one sample was excluded in the statistics due to incomplete data). ∗P < 0.05, HFD versus ND; Student's t-test; Two-way ANOVA, followed by Bonferroni post hoc comparison test.

Figure 4

Lipid peroxidation profile indicating MDA concentration in (a) placenta, (b) liver tissues of GD19 and PP21 dams, (c) liver of male and (d) female offspring rats at PND 21, 28 and 35. Data shown represents mean ± SEM; n = 6 per group. ∗P < 0.05, ∗∗∗P < 0.0001 compared to ND; ^ɸP < 0.05 compared to HFD; ^‡P < 0.05, ND/QR vs. HFD/QR; One-Way or Two-way ANOVA, followed by Bonferroni post hoc comparison test.

Figure 5

Concentration of NO in (a) placenta, (b) liver tissues of GD21 and PP21 dams, (c) liver of male and (d) female offspring rats at PND 21, 28 and 35. Data shown represents mean ± SEM; n = 6 per group. ∗P < 0.05, ∗∗∗P < 0.001 compared to ND; ^ɸP < 0.05 compared to HFD; One-Way or Two-way ANOVA, followed by Bonferroni post hoc comparison test.

Figure 6

The above graphs indicate correlation between (a) MDA levels in PND21 offspring liver and placenta. Also, insignificant relationship between placenta MDA and liver NO production in (b) PP21 dams (c) PND 28 and (d) PND 35 offspring were observed.