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Increased Susceptibility to Obesity and Glucose Intolerance in Adult Female Rats Programmed by High-Protein Diet during Gestation, But Not during Lactation.

ABSTRACT: Fetal and early postnatal nutritional environments contribute to lifelong health. High-protein (HP) intake in early life can increase obesity risk in response to specific feeding conditions after weaning. This study investigated the effects of a maternal HP diet during pregnancy and/or lactation on the metabolic health of offspring. Three groups of dams received a normal-protein (NP, 20E% proteins) diet during gestation and lactation (Control group), an HP diet (55E% proteins) during gestation (HPgest group), or an HP diet during lactation (HPlact group). From weaning until 10 weeks, female pups were exposed to the NP, the HP or the western (W) diet. HPgest pups had more adipocytes (p = 0.009), more subcutaneous adipose tissue (p = 0.04) and increased expression of genes involved in liver fatty acid synthesis at 10 weeks (p < 0.05). HPgest rats also showed higher food intake and adiposity under the W diet compared to the Control and HPlact rats (p ? 0.04). The post-weaning HP diet reduced weight (p < 0.0001), food intake (p < 0.0001), adiposity (p < 0.0001) and glucose tolerance (p < 0.0001) compared to the NP and W diets; this effect was enhanced in the HPgest group (p = 0.04). These results show that a maternal HP diet during gestation, but not lactation, leads to a higher susceptibility to obesity and glucose intolerance in female offspring.

SUBMITTER: Desclee de Maredsous C

PROVIDER: S-EPMC7071251 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Increased Susceptibility to Obesity and Glucose Intolerance in Adult Female Rats Programmed by High-Protein Diet during Gestation, But Not during Lactation.

Desclée de Maredsous Caroline C Carlin Gabrielle G Oosting Annemarie A Delteil Corine C Azzout-Marniche Dalila D Chaumontet Catherine C Blachier François F Barbillon Pierre P Mary-Huard Tristan T Tomé Daniel D Oozeer Raish R Davila Anne-Marie AM

Nutrients 20200125 2

Fetal and early postnatal nutritional environments contribute to lifelong health. High-protein (HP) intake in early life can increase obesity risk in response to specific feeding conditions after weaning. This study investigated the effects of a maternal HP diet during pregnancy and/or lactation on the metabolic health of offspring. Three groups of dams received a normal-protein (NP, 20E% proteins) diet during gestation and lactation (Control group), an HP diet (55E% proteins) during gestation ( ...[more]

PMID: 31991777

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Project description:Using female Sprague-Dawley (SD) rats as a model, the current study aimed to investigate whether feeding 5-aminolevulinic acid (5-ALA) to female SD rats during gestation and lactation can affect the iron status of weaned rats and provide new ideas for the iron supplementation of piglets. A total of 27 pregnant SD rats were randomly assigned to three treatments in nine replicates, with one rat per litter. Dietary treatments were basal diet (CON), CON + 50 mg/kg 5-ALA (5-ALA50), and CON + 100 mg/kg 5-ALA (5-ALA100). After parturition, ten pups in each litter (a total of 270) were selected for continued feeding by their corresponding mother, and the pregnant rats were fed diets containing 5-ALA (0, 50 and 100 mg/kg diet) until the newborn pups were weaned at 21 days. The results showed that the number of red blood cells (RBCs) in weaned rats in the 5-ALA100 group was significantly higher (p < 0.05) than that in the CON or 5-ALA50 group. The diet with 5-ALA significantly increased (p < 0.05) the hemoglobin (HGB) concentration, hematocrit (HCT) level, serum iron (SI) content, and transferrin saturation (TSAT) level in the blood of weaned rats, as well as the concentration of Hepcidin in the liver and serum of weaned rats and the expression of Hepcidin mRNA in the liver of weaned rats, with the 5-ALA100 group having the highest (p < 0.05) HGB concentration in the weaned rats, and the 5-ALA50 group having the highest (p < 0.05) Hepcidin concentration in serum and in the expression of Hepcidin mRNA in the liver of weaned rats. The other indicators between the 5-ALA groups had no effects. However, the level of total iron binding capacity (TIBC) was significantly decreased (p < 0.05) in the 5-ALA50 group. Moreover, the iron content in the liver of weaned rats fed with 5-ALA showed an upward trend (p = 0.085). In addition, feeding a 5-ALA-supplemented diet could also significantly reduce (p < 0.05) the expression of TfR1 mRNA in the liver of weaning rats (p < 0.05), and the expression of Tfr1 was not affected between 5-ALA groups. In conclusion, dietary supplementation with 5-ALA could improve the blood parameters, increase the concentration of Hepcidin in the liver and serum, and affect the expression of iron-related genes in the liver of weaned rats. Moreover, it is appropriate to add 50 mg/kg 5-ALA to the diet under this condition.

Project description:ObjectiveExposure to persistent organic pollutants is consistently associated with increased diabetes risk in humans. We investigated the short- and long-term impact of transient low-dose dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life.MethodsFemale mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy and lactation, and then tracked for 6-10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams was then transferred to a 45% high-fat diet (HFD) or remained on a standard chow diet for an additional 11 weeks to assess the long-term effects of TCDD on adaptability to a metabolic stressor. To summarize, female mice were transiently exposed to TCDD and then subsequently tracked beyond when TCDD had been excreted to identify lasting metabolic effects of TCDD exposure.ResultsTCDD-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-TCDD exposure. However, TCDD-exposed dams on a chow diet were modestly heavier than controls starting 5 weeks after the last TCDD injection, and their weight gain accelerated after transitioning to a HFD. TCDD-exposed dams also had an accelerated onset of hyperglycemia, impaired glucose-induced plasma insulin levels, reduced islet size, increased MAFA-ve beta cells, and increased proinsulin accumulation following HFD feeding compared to controls. Overall, our study demonstrates that low-dose TCDD exposure during pregnancy has minimal effects on metabolism during the period of active exposure, but has detrimental long-term effects on metabolic adaptability to HFD feeding.ConclusionsOur study suggests that transient low-dose TCDD exposure in female mice impairs metabolic adaptability to HFD feeding, demonstrating that dioxin exposure may be a contributing factor to obesity and diabetes pathogenesis in females.

Dataset Information

Increased Susceptibility to Obesity and Glucose Intolerance in Adult Female Rats Programmed by High-Protein Diet during Gestation, But Not during Lactation.

Publications

Increased Susceptibility to Obesity and Glucose Intolerance in Adult Female Rats Programmed by High-Protein Diet during Gestation, But Not during Lactation.

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