No abstract

No abstract

We aimed to analyze the long-term metabolic effects of leptin supplementation at physiological doses during suckling in the offspring of diet-induced obese rats, together with the potential benefits of improving maternal diet during lactation. Thus, the offspring of: dams fed standard-diet (SD) (CON-dams), dams fed western-diet (WD) before and during gestation and lactation (WD-dams), and dams fed as WD-dams but moved to SD during lactation (REV-dams) were supplemented throughout suckling with leptin or vehicle, and fed SD or WD from weaning to four months. Under SD, leptin treatment significantly improved metabolic profile and body fat accumulation, with stronger effects in the male offspring of CON-dams and REV-dams. Under WD, the offspring of WD-dams presented metabolic alterations that were not evident in the offspring of REV-dams. Moreover, leptin supplementation improved glucose homeostasis in the male offspring of REV-dams. Conversely, leptin supplementation in females born to WD-dams and fed WD from weaning resulted in impaired insulin sensitivity and increased hepatic lipid content. These results highlight the importance of a balanced maternal diet during the perinatal period, especially lactation, for the subsequent metabolic health of the offspring and for the beneficial effects of leptin supplementation during suckling, more evident in the male offspring.

This study aims to assess in rats whether normalizing maternal diet during lactation prevents the harmful effects of western diet (WD) consumption during the whole perinatal period on the lipidomic profile in maternal milk and offspring plasma. Methods and Results: Control dams (CON-dams), fed with standard diet (SD); WD-dams, fed with WD prior and during gestation and lactation; and reversion dams (REV-dams), fed as WD-dams but moved to SD during lactation are followed. Lipidomic analysis is performed in milk and plasma samples from pups. Milk of WD-dams presents a different triacylglycerol composition and free fatty acid (FA) profile compared to CON-dams, including an increased ratio of pro-inflammatory to anti-inflammatory long-chain polyunsaturated FA. Such alterations, which are also present in the plasma of their offspring, are widely reversed in the milk of REV-dams and the plasma of their pups. This is related with the recovery of control adiponectin expression levels in the mammary gland, and the presence of decreased expression of pro-inflammatory factors. Conclusion: Implementing a healthy diet during lactation prevents early alterations in the plasma lipidome of pups associated to the maternal intake of an obesogenic diet, which may be related to the normalization of milk lipid content and the inflammatory state in the mammary gland.

Scope To examine the effects of myo‐inositol supplementation during lactation in male and female rats on metabolic parameters and its potential to reverse metabolic alterations associated with a moderate gestational calorie restriction. Methods and results The offspring of control and 25% gestational calorie‐restricted rats are supplemented with myo‐inositol or vehicle throughout lactation and exposed to a Western diet (WD) from 5 to 7 months of age. Blood parameters are measured and gene expression and protein levels in retroperitoneal white adipose tissue (rWAT) and liver are analyzed. In male offspring, but not in females, myo‐inositol supplementation resulted in lower fasting triglyceride and insulin levels and HOMA‐IR at 7 months, and reversed the alterations in these parameters due to gestational calorie restriction. The expression pattern of key genes in metabolism in rWAT and liver support the beneficial effect of myo‐inositol supplementation in reversing metabolic alterations programmed by gestational calorie restriction in male rats. Conclusions Myo‐inositol supplementation at physiological doses during lactation improves metabolic health and prevents the programmed trend to develop insulin resistance and hypertriglyceridemia in male rats acquired by inadequate fetal nutrition and exacerbated by a diabetogenic diet in adulthood. The absence of clear effects in females deserves further investigation.

We studied whether myo-inositol supplementation throughout lactation, alone and combined with leptin, may reverse detrimental effects on hypothalamic structure and function caused by gestational calorie gestation (CR) in rats. Candidate early transcript-based biomarkers of metabolic health in peripheral blood mononuclear cells (PBMC) were also studied. Offspring of dams exposed to 25% gestational CR and supplemented during lactation with physiological doses of leptin (CR-L), myo-inositol (CR-M), the combination (CR-LM), or the vehicle (CR-V) as well as control rats (CON-V) were followed and sacrificed at postnatal day 25. Myo-inositol and the combination increased the number of neurons in arcuate nucleus (ARC) (only in females) and paraventricular nucleus, and myo-inositol (alone) restored the number of αMSH+ neurons in ARC. Hypothalamic mRNA levels of Lepr in CR-M and Insr in CR-M and CR-LM males were higher than in CR-V and CON-V, respectively. In PBMC, increased expression levels of Lrp11 and Gls in CR-V were partially normalized in all supplemented groups (but only in males for Gls). Therefore, myo-inositol supplementation throughout lactation, alone and combined with leptin, reverts programmed alterations by fetal undernutrition on hypothalamic structure and gene expression of potential early biomarkers of metabolic health in PBMC, which might be attributed, in part, to increased leptin sensitivity.

We aimed to evaluate in rats whether the levels of specific miRNA are altered in the mammary gland (MG) and milk of diet-induced obese dams, and whether improving maternal nutrition during lactation attenuates such alterations. Dams fed with a standard diet (SD) (control group), with a Western diet (WD) prior to and during gestation and lactation (WD group), or with WD prior to and during gestation but moved to SD during lactation (Rev group) were followed. The WD group showed higher miR-26a, miR-222 and miR-484 levels than the controls in the MG, but the miRNA profile in Rev animals was not different from those of the controls. The WD group also displayed higher miR-125a levels than the Rev group. Dams of the WD group, but not the Rev group, displayed lower mRNA expression levels of Rb1 (miR-26a’s target) and Elovl6 (miR-125a’s target) than the controls in the MG. The WD group also presented lower expression of Insig1 (miR-26a’s target) and Cxcr4 (miR-222’s target) than the Rev group. However, both WD and Rev animals displayed lower expression of Vegfa (miR-484’s target) than the controls. WD animals also showed greater miR-26a, miR-125a and miR-222 levels in the milk than the controls, but no differences were found between the WD and Rev groups. Thus, implementation of a healthy diet during lactation normalizes the expression levels of specific miRNAs and some target genes in the MG of diet-induced obese dams but not in milk.

We aimed to evaluate whether improving maternal diet during lactation in diet‐induced obese rats reverts the impact of western diet (WD) consumption on the metabolome of milk and offspring plasma, as well as to identify potential biomarkers of these conditions. Three groups of dams were followed: control‐dams (CON‐dams), fed with standard diet (SD); WD‐dams, fed with WD prior and during gestation and lactation; and reversion‐dams (REV‐dams), fed as WD‐dams but moved to SD during lactation. Metabolomic analysis was performed in milk at lactation days 5, 10, and 15, and in plasma from their male and female offspring at postnatal day 15. Milk of WD‐dams presented, throughout lactation and compared to CON‐dams, altered profiles of amino acids and of the carnitine pool, accompanied by changes in other polar metabolites, being stachydrine, N‐acetylornithine, and trimethylamine N‐oxide the most relevant and discriminatory metabolites between groups. The plasma metabolome profile was also altered in the offspring of WD‐dams in a sex‐dependent manner, and stachydrine, ergothioneine and the acylcarnitine C12:1 appeared as the top three most discriminating metabolites in both sexes. Metabolomic changes were largely normalized to control levels both in the milk of REV‐dams and in the plasma of their offspring. We have identified a set of polar metabolites in maternal milk and in the plasma of the offspring whose alterations may indicate maternal intake of an unbalanced diet during gestation and lactation. Levels of these metabolites may also reflect the beneficial effects of implementing a healthier diet during lactation.