Maternal supplementation with chia oil attenuates hepatic metabolic disturbances in mice subjected to postnatal undernutrition

Abstract

Background: Early postnatal undernutrition, leading to impaired growth and low body weight, has been associated with enduring metabolic alterations that may persist into adulthood. We proposed that plant-based ω-3 fatty acids, as in maternal supplementation, attenuate metabolic alterations induced by postnatal dietary restriction, such as glucose disturbances and oxidative stress.

Methods: To test this, we investigated the effects of maternal supplementation with two distinct doses of Chia Oil (ChO) (2.5 or 5 g/kg body mass) on metabolic parameters in BALB/c mice subjected to postnatal undernutrition. The undernutrition model was created by increasing the litter size to 15-16 pups, forming the undernutrition (UN) group. These UN groups received maternal ChO supplementation at 2.5 g/kg or 5 g/kg b.m., labeled as UN2.5 and UN5, respectively.

Results: By day 21, the UN5 group showed less weight gain compared to the UN2.5 group. At 120 days, glucose tolerance tests revealed a lower area under the curve in both supplemented groups compared to the UN animals. A maternal dose of 5 g/kg b.m. of ChO was linked to more favorable oxidative stress markers, suggesting this effect is not due to changes in antioxidant enzymes like superoxide dismutase and catalase, which remained stable in the liver tissue in this model. This dose provided a slight benefit in reducing metabolic changes, with the UN5 group showing lower total hepatic lipid levels. Additionally, histopathological analysis of the tissue revealed no alterations in the experimental groups.

Conclusion: These observations suggest a protective role of maternal ChO supplementation at a dose of 5 g/kg b.w. against metabolic impairments induced by postnatal undernutrition.

Keywords: alpha-linolenic acid; fetal development; malnutrition; omega-3; oxidative stress.

Figure 1

Experimental design. Pregnant female mice were housed in groups of three, each paired with a male for mating, and which the males were removed. Following birth, the litter sizes were adjusted based on the experimental group requirements. Only male pups were used in the study. The oral glucose tolerance test was conducted at 70 and 120 days post-birth to assess glucose levels. Additionally, lipid profiles, histological parameters, and oxidative stress were evaluated. C, control; UN, undernutrition group; UN2.5, undernutrition group with chia oil (2.5 g/kg b.m.) supplementation; UN5, undernutrition group with chia oil (5 g/kg b.m.) supplementation; b.m., body mass.

Figure 2

Postnatal undernutrition leads to a lower body mass than the control litter at 21, 70, and 120 days. Data are presented as mean ± standard error of the mean. *p < 0.05 vs. C. ^#p < 0.05 vs. UN2.5. Data were analyzed using one-way analysis of variance, followed by Bonferroni post hoc test. Control (C, n = 9), undernutrition (UN, n = 5), undernutrition with 2.5 g/kg b.m. chia oil supplementation (UN2.5, n = 8), and undernutrition with 5 g/kg b.m. Chia oil supplementation (UN5, n = 10).

Figure 3

No significant differences in glycemic response were observed among the groups at 70 days (A, B). The undernutrition litters from females supplemented with chia oil exhibited lower glycemic curves at 30, 60, 90, and 120 min (C) and lower glucose concentration at 120 days (D) compared to the undernutrition litter control. Data are presented as mean ± standard error of the mean. *p < 0.05 vs. C. ^#p < 0.05 vs. UN. The data were analyzed using a one-way analysis of variance followed by the Bonferroni post hoc test. Control (C, n = 9), undernutrition (UN, n = 5), undernutrition with 2.5 g/kg b.m. Chia oil supplementation (UN2.5, n = 8), and undernutrition with 5 g/kg b.m. Chia oil supplementation (UN5, n = 10).

Figure 4

Histological sections of the liver were stained with hematoxylin and eosin (H&E). Central lobular region. (A) Control Group with multifocal areas of discrete vacuolization in the cytoplasm of hepatocytes (arrow); (B) undernutrition Group with moderate vacuolization in the cytoplasm of hepatocytes (arrows). (C) Undernutrition with 2.5 g/kg b.m. chia oil supplementation and (D) undernutrition with 5 g/kg b.m. chia oil supplementation with multifocal areas of discrete vacuolation in the cytoplasm of hepatocytes (arrow). Scale bars: 50 μm.

Figure 5

Maternal supplementation with chia oil influences the oxidant profile in the liver of undernourished offspring. The UN5 group exhibited lower TBARS and hydroperoxide levels (A, B). The UN2.5 group exhibited higher CAT and SOD activities (C, D). Data are presented as mean ± standard error of the mean. *p < 0.05; **p < 0.01; ***p < 0.001. The data were analyzed using a one-way analysis of variance followed by the Bonferroni post hoc test. Control (C, n = 9), Undernutrition (UN, n = 5), Undernutrition with 2.5 g/kg b.m. Chia oil supplementation (UN2.5, n = 8), and Undernutrition with 5 g/kg b.m. Chia oil supplementation (UN5, n = 10).

Figure 6

Maternal chia oil supplementation affects the oxidant profile of undernourished offspring in the epididymal adipose tissue. The UN2.5 and UN5 litters exhibited lower TBARS concentrations (A). UN 2.5 exhibited higher hydroperoxide levels, while UN 5 showed lower levels (B). Catalase activity was higher in the UN2.5 group (C). No significant changes were observed in SOD activity (D). Data are presented as mean ± standard error of the mean. *p < 0.05; **p < 0.01; ***p < 0.001. The data were analyzed using a one-way analysis of variance followed by the Bonferroni post hoc test. Control (C, n = 9), Undernutrition (UN, n = 5), Undernutrition with 2.5 g/kg b.m. Chia oil supplementation (UN2.5, n = 8), and Undernutrition with 5 g/kg b.m. Chia oil supplementation (UN5, n = 10).