Maternal Dietary Improvement or Leptin Supplementation During Suckling Mitigates the Long-Term Impact of Maternal Obesogenic Conditions on Inflammatory and Oxidative Stress Biomarkers in the Offspring of Diet-Induced Obese Rats

Abstract

This study investigates the impact of maternal nutrition during lactation on inflammation and oxidative stress in the offspring of diet-induced obese rats, along with the potential benefits of leptin supplementation during suckling. Dams were fed either a standard diet (SD), a western diet (WD) before and during gestation and lactation (WD-dams), or a WD switched to an SD during lactation (Rev-dams). Offspring were supplemented with leptin or vehicle during suckling and then fed an SD or WD until four months. Offspring of the Rev-dams exhibited improved metabolic indicators, including lower body weight, reduced plasma levels of TNF-alpha, a higher adiponectin/leptin (A/L) ratio, enhanced liver antioxidant defenses, and decreased inflammation markers in white adipose tissue (WAT) compared to WD-dams, with sex differences. Leptin supplementation further modulated these markers, reducing oxidative stress in liver and inflammation in WAT and liver (e.g., hepatic Tnfa expression decreased by 45% (males) and 41% (females) in the WD group on an SD), and improving the A/L ratio, with effects varying by maternal conditions and sex. In conclusion, this study underscores the importance of maternal nutrition and leptin intake during suckling in shaping long-term metabolic and inflammatory health in offspring, offering strategies to mitigate the adverse effects of maternal obesity on future generations.

Keywords: antioxidant defenses; inflammation; lactation; leptin; maternal nutrition; metabolic programming.

Figure 1

Circulating parameters of O-C, O-WD, and O-Rev male and female animals treated with vehicle or leptin during suckling and fed an SD or WD from weaning, at four months of age. Data are presented as the mean ± SEM (n = 8–12). Statistics: After data separation depending on post-weaning diet, three-way ANOVA was performed to analyze the effects of sex, maternal diet, and/or leptin treatment. In each sex, two-way ANOVA was performed to analyze the effects of leptin treatment and/or maternal diet. Single comparisons between leptin- and vehicle-treated rats of all experimental groups were carried out using the Mann–Whitney U test. Symbols: sex (S), maternal diet (MD), leptin treatment (L); Data that do not share a letter are significantly different, A ≠ B (p < 0.05, LSD post hoc, two- or three-way ANOVA); *, different from their vehicle-treated equal (p < 0.05, Mann–Whitney U test). Abbreviations: offspring of C-dams (O-C), offspring of WD-dams (O-WD), offspring of Rev-dams (O-Rev), vehicle (Veh), leptin (Lep).

Figure 2

Expression levels of genes related to inflammation in retroperitoneal white adipose tissue of O-C, O-WD, and O-Rev male and female animals treated with vehicle or leptin during suckling and fed an SD or WD from weaning, at four months of age. Data are presented as the mean ± SEM (n = 8–12) and are expressed as a percentage of the value for the O-C male rats. Statistics: After data separation depending on post-weaning diet, three-way ANOVA was performed to analyze the effects of sex, maternal diet, and/or leptin treatment. In each sex, two-way ANOVA was performed to analyze the effects of leptin treatment and/or maternal diet. Single comparisons between leptin- and vehicle-treated rats of all experimental groups were carried out using the Mann–Whitney U test. Symbols: sex (S), maternal diet (MD), leptin treatment (L); Data that do not share a letter are significantly different, A ≠ B (p < 0.05, LSD post hoc, two- or three-way ANOVA); *, different from their vehicle-treated equal (p < 0.05, Mann–Whitney U test). Abbreviations: offspring of C-dams (O-C), offspring of WD-dams (O-WD), offspring of Rev-dams (O-Rev), vehicle (Veh), leptin (Lep).

Figure 3

Expression levels of genes related to inflammation in liver of O-C, O-WD, and O-Rev male and female animals treated with vehicle or leptin during suckling and fed an SD or WD from weaning, at four months of age. Data are presented as the mean ± SEM (n = 8–12) and are expressed as a percentage of the value for the O-C male rats. Statistics: After data separation depending on post-weaning diet, three-way ANOVA was performed to analyze the effects of sex, maternal diet, and/or leptin treatment. In each sex, two-way ANOVA was performed to analyze the effects of leptin treatment and/or maternal diet. Single comparisons between leptin- and vehicle-treated rats of all experimental groups were carried out using the Mann–Whitney U test. Symbols: sex (S), maternal diet (MD), leptin treatment (L); Data that do not share a letter are significantly different, A ≠ B (p < 0.05, LSD post hoc, two- or three-way ANOVA); *, different from their vehicle-treated equal (p < 0.05, Mann–Whitney U test). Abbreviations: offspring of C-dams (O-C), offspring of WD-dams (O-WD), offspring of Rev-dams (O-Rev), vehicle (Veh), leptin (Lep).

Figure 4

Markers of antioxidant defenses in the liver of O-C, O-WD, and O-Rev male and female animals treated with vehicle or leptin during suckling and fed an SD or WD from weaning, at four months of age. Data are presented as the mean ± SEM (n = 8–12). Statistics: After data separation, depending on the post-weaning diet, three-way ANOVA was performed to analyze the effects of sex, maternal diet, and/or leptin treatment. In each sex, two-way ANOVA was performed to analyze the effects of leptin treatment and/or maternal diet. Single comparisons between leptin- and vehicle-treated rats for all experimental groups were carried out using the Mann–Whitney U test. Sex (S), maternal diet (MD), and leptin treatment (L); Data that do not share a letter are significantly different, A ≠ B ≠ C (p < 0.05, LSD post hoc and two- or three-way ANOVA); * different from their vehicle-treated equal (p < 0.05, Mann–Whitney U test). Offspring of C-dams (O-C), offspring of WD-dams (O-WD), offspring of Rev-dams (O-Rev), vehicle (Veh), and leptin (Lep).

Figure 5

Summary of the main long-term effects of maternal conditions during suckling on O-C, O-WD, and O-Rev male and female animals weaned onto an SD or WD. Offspring of C-dams (O-C), offspring of WD-dams (O-WD), and offspring of Rev-dams (O-Rev). Arrows indicate increases (↑) or decreases (↓) according to a two-way or three-way ANOVA. Red arrows represent negative effects, while blue arrows indicate positive effects.

Figure 6

Summary of the main long-term effects of leptin supplementation during suckling on O-C, O-WD, and O-Rev male and female animals weaned onto an SD or WD. Offspring of C-dams (O-C), offspring of WD-dams (O-WD), and offspring of Rev-dams (O-Rev). Arrows indicate increases (↑) or decreases (↓) according to a Mann–Whitney U test, two-way or three-way ANOVA. Red arrows represent negative effects, while blue arrows indicate positive effects.