Lean Mothers Research Articles

The interplay of maternal and offspring obesogenic diets: the impact on offspring metabolism and muscle mitochondria in an outbred mouse model.

Consumption of obesogenic (OB) diets increases the prevalence of maternal obesity worldwide, causing major psychological and social burdens in women. Obesity not only impacts the mother's health and fertility but also elevates the risk of obesity and metabolic disorders in the offspring. Family lifestyle is mostly persistent through generations, possibly contributing to the growing prevalence of obesity. We hypothesized that offspring metabolic health is dependent on both maternal and offspring diet and their interaction. We also hypothesized that the sensitivity of the offspring to the diet may be influenced by the match or mismatch between offspring and maternal diets. To test these hypotheses, outbred Swiss mice were fed a control (C, 10% fat, 7% sugar, and n = 14) or OB diet (60% fat, 20% sugar, and n = 15) for 7 weeks and then mated with the same control males. Mice were maintained on the same corresponding diet during pregnancy and lactation, and the offspring were kept with their mothers until weaning. The study focused only on female offspring, which were equally distributed at weaning and fed C or OB diets for 7 weeks, resulting in four treatment groups: C-born offspring fed C or OB diets (C » C and C » OB) and OB-born offspring fed C or OB diets (OB » C and OB » OB). Adult offspring's systemic blood profile (lipid and glucose metabolism) and muscle mitochondrial features were assessed. We confirmed that the offspring's OB diet majorly impacted the offspring's health by impairing the offspring's serum glucose and lipid profiles, which are associated with abnormal muscle mitochondrial ultrastructure. Contrarily, maternal OB diet was associated with increased expression of mitochondrial complex markers and mitochondrial morphology in offspring muscle, but no additive effects of (increased sensitivity to) an offspring OB diet were observed in pups born to obese mothers. In contrast, their metabolic profile appeared to be healthier compared to those born to lean mothers and fed an OB diet. These results are in line with the thrifty phenotype hypothesis, suggesting that OB-born offspring are better adapted to an environment with high energy availability later in life. Thus, using a murine outbred model, we could not confirm that maternal obesogenic diets contribute to female familial obesity in the following generations.

The Concentration of Lactoferrin in Breast Milk Correlates with Maternal Body Mass Index and Parity.

Background: Lactoferrin (LF) is a multifunctional glycoprotein found in human milk and body fluids, which has been shown to play a vital role in regulating the immunity and supporting the intestinal health of infants. Aim: This study evaluated the association between maternal/parturient factors and LF concentration in the breast milk of Chinese mothers. Methods: 207 breast milk samples were collected from healthy mothers with in the first year of lactation. Maternal and parturient information was collected for these participants through questionnaires. The content of lactoferrin in breast milk was detected by liquid chromatography, and macronutrient concentration in breast milk was measured by human milk analyzer in only 109 samples. Results: Our findings demonstrated that the LF content was much higher within the first month of lactation than it was after that period (p < 0.05). When compared with normal and lean mothers, the LF content of obese mothers was considerably higher (p < 0.05). The parity and LF content showed a favorable correlation. The proportion of LF to total protein tended to decrease as lactation progressed. Protein, fat, dry matter, and energy content were significantly positively correlated with LF content (p < 0.001). Conclusion: Early breast milk tends to have a higher level of LF, and the change of LF concentration in breast milk is associated with the parity and body mass index of the mother.

Maternal obesity damages the median eminence blood-brain barrier structure and function in the progeny: the beneficial impact of cross-fostering by lean mothers.

Maternal obesity is an important risk factor for obesity, cardiovascular, and metabolic diseases in the offspring. Studies have shown that it leads to hypothalamic inflammation in the progeny, affecting the function of neurons regulating food intake and energy expenditure. In adult mice fed a high-fat diet, one of the hypothalamic abnormalities that contribute to the development of obesity is the damage of the blood-brain barrier (BBB) at the median eminence-arcuate nucleus (ME-ARC) interface; however, how the hypothalamic BBB is affected in the offspring of obese mothers requires further investigation. Here, we used confocal and transmission electron microscopy, transcript expression analysis, glucose tolerance testing, and a cross-fostering intervention to determine the impact of maternal obesity and breastfeeding on BBB integrity at the ME-ARC interface. The offspring of obese mothers were born smaller; conversely, at weaning, they presented larger body mass and glucose intolerance. In addition, maternal obesity-induced structural and functional damage of the offspring's ME-ARC BBB. By a cross-fostering intervention, some of the defects in barrier integrity and metabolism seen during development in an obesogenic diet were recovered. The offspring of obese dams breastfed by lean dams presented a reduction of body mass and glucose intolerance as compared to the offspring continuously exposed to an obesogenic environment during intrauterine and perinatal life; this was accompanied by partial recovery of the anatomical structure of the ME-ARC interface, and by the normalization of transcript expression of genes coding for hypothalamic neurotransmitters involved in energy balance and BBB integrity. Thus, maternal obesity promotes structural and functional damage of the hypothalamic BBB, which is, in part, reverted by lactation by lean mothers.NEW & NOTEWORTHY Maternal dietary habits directly influence offspring health. In this study, we aimed at determining the impact of maternal obesity on BBB integrity. We show that DIO offspring presented a leakier ME-BBB, accompanied by changes in the expression of transcripts encoding for endothelial and tanycytic proteins, as well as of hypothalamic neuropeptides. Breastfeeding in lean dams was sufficient to protect the offspring from ME-BBB disruption, providing a preventive strategy of nutritional intervention during early life.

A cross-sectional study evidences regulations of leukocytes in the colostrum of mothers with obesity

BackgroundBreastmilk is a dynamic fluid whose initial function is to provide the most adapted nutrition to the neonate. Additional attributes have been recently ascribed to breastmilk, with the evidence of a specific microbiota and the presence of various components of the immune system, such as cytokines and leukocytes. The composition of breastmilk varies through time, according to the health status of mother and child, and altogether contributes to the future health of the infant. Obesity is a rising condition worldwide that creates a state of systemic, chronic inflammation including leukocytosis. Here, we asked whether colostrum, the milk produced within the first 48 h post-partum, would contain a distinct leukocyte composition depending on the body mass index (BMI) of the mother.MethodsWe collected peripheral blood and colostrum paired samples from obese (BMI > 30) and lean (BMI < 25) mothers within 48 h post-partum and applied a panel of 6 antibodies plus a viability marker to characterize 10 major leukocyte subpopulations using flow cytometry.ResultsThe size, internal complexity, and surface expression of CD45 and CD16 of multiple leukocyte subpopulations were selectively regulated between blood and colostrum irrespective of the study groups, suggesting a generalized cell-specific phenotype alteration. In obesity, the colostrum B lymphocyte compartment was significantly reduced, and CD16+ blood monocytes had an increased CD16 expression compared to the lean group.ConclusionsThis is the first characterization of major leukocyte subsets in colostrum of mothers suffering from obesity and the first report of colostrum leukocyte subpopulations in Latin America. We evidence various significant alterations of most leukocyte populations between blood and colostrum and demonstrate a decreased colostrum B lymphocyte fraction in obesity. This pioneering study is a stepping stone to further investigate active immunity in human breastmilk.

Maternal obesity: new placental paradigms unfolded.

The prevalence of maternal obesity is increasing at an alarming rate, and is providing a major challenge for obstetric practice. Adverse effects on maternal and fetal health are mediated by complex interactions between metabolic, inflammatory, and oxidative stress signaling in the placenta. Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are common downstream pathways of cell stress, and there is evidence that this conserved homeostatic response may be a key mediator in the pathogenesis of placental dysfunction. We summarize the current literature on the placental cellular and molecular changes that occur in obese women. A special focus is cast onto placental ER stress in obese pregnancy, which may provide a novel link for future investigation.

Impact of Maternal Obesity on the Gestational Metabolome and Infant Metabolome, Brain, and Behavioral Development in Rhesus Macaques.

Maternal gestational obesity is associated with elevated risks for neurodevelopmental disorder, including autism spectrum disorder. However, the mechanisms by which maternal adiposity influences fetal developmental programming remain to be elucidated. We aimed to understand the impact of maternal obesity on the metabolism of both pregnant mothers and their offspring, as well as on metabolic, brain, and behavioral development of offspring by utilizing metabolomics, protein, and behavioral assays in a non-human primate model. We found that maternal obesity was associated with elevated inflammation and significant alterations in metabolites of energy metabolism and one-carbon metabolism in maternal plasma and urine, as well as in the placenta. Infants that were born to obese mothers were significantly larger at birth compared to those that were born to lean mothers. Additionally, they exhibited significantly reduced novelty preference and significant alterations in their emotional response to stress situations. These changes coincided with differences in the phosphorylation of enzymes in the brain mTOR signaling pathway between infants that were born to obese and lean mothers and correlated with the concentration of maternal plasma betaine during pregnancy. In summary, gestational obesity significantly impacted the infant systemic and brain metabolome and adaptive behaviors.

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

BackgroundMaternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring.MethodsFemale C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint.ResultsOffspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress.ConclusionGestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.

Phenotypic and Epigenetic Adaptations of Cord Blood CD4+ T Cells to Maternal Obesity.

Pregravid obesity has been shown to disrupt the development of the offspring’s immune system and increase susceptibility to infection. While the mechanisms underlying the impact of maternal obesity on fetal myeloid cells are emerging, the consequences for T cells remain poorly defined. In this study, we collected umbilical cord blood samples from infants born to lean mothers and mothers with obesity and profiled CD4 T cells using flow cytometry and single cell RNA sequencing at resting and following ex vivo polyclonal stimulation. We report that maternal obesity is associated with higher frequencies of memory CD4 T cells suggestive of in vivo activation. Moreover, single cell RNA sequencing revealed expansion of an activated subset of memory T cells with maternal obesity. However, ex vivo stimulation of purified CD4 T cells resulted in poor cytokine responses, suggesting functional defects. These phenotypic and functional aberrations correlated with methylation and chromatin accessibility changes in loci associated with lymphocyte activation and T cell receptor signaling, suggesting a possible link between maternal obesogenic environment and fetal immune reprogramming. These observations offer a potential explanation for the increased susceptibility to microbial infection in babies born to mothers with obesity.

Maternal Overweight vs. Polycystic Ovary Syndrome: Disentangling Their Impact on Insulin Action in Pregnancy-A Prospective Study.

Background: To investigate insulin sensitivity and glucose metabolism in pregnant lean and overweight polycystic ovary syndrome (PCOS) patients vs. lean and overweight controls without PCOS. Methods: Prospective cohort study on 67 pregnant women (31 with PCOS and 36 controls, subdivided into overweight or obese and normal weight). All women underwent a 2h-OGTT including glucose, insulin, and C-peptide in early- and mid-gestation and were followed-up until delivery. Results: Insulin sensitivity and glucometabolic parameters were comparable between PCOS patients and controls, whereas marked differences were observed between overweight/obese and lean mothers. Impaired whole-body insulin sensitivity at early pregnancy is mainly a consequence of higher BMI (body mass index; p < 0.001) compared to PCOS (p = 0.216), whereby no interaction between overweight/obesity and PCOS was observed (p = 0.194). Moreover, overweight was significantly associated with gestational diabetes (p = 0.0003), whereas there were no differences between women with and without PCOS (p = 0.51). Birth weight was inversely related to whole-body insulin sensitivity (rho = −0.33, p = 0.014) and positively associated with higher pregestational BMI (rho = 0.33, p = 0.012), whereas there was no association with PCOS. Conclusions: Impaired insulin action was mainly a consequence of overweight rather than PCOS. Our data suggest that overweight is more relevant than PCOS for the effects on insulin sensitivity and impaired glucose metabolism.

Familial Obesity Risk and Current Excess Weight Influence Brain Structure in Adolescents.

Obesity risk transmits from parents to children. Underlying neural mechanisms were investigated in this study by evaluating influences of familial obesity risk defined by maternal obesity and influences of current overweight on three indices of brain structure in adolescents. In total, 22 lean adolescents with lean mothers (lean low-risk), 25 lean adolescents with mothers with obesity/overweight (lean high-risk), and 36 adolescents with obesity/overweight underwent structural MRI scans for estimation of regional gray and white matter volume and cortical thickness. The lean high-risk compared with the lean low-risk group demonstrated lower gray and white matter volume and cortical thickness in the postcentral gyrus (somatosensory cortex), lower gray and white matter volume in the opercular cortex (taste cortex), lower gray matter volume and cortical thickness in the anterior cingulate cortex, and lower cortical thickness in the precuneus. Comparisons of the lean and obesity/overweight groups revealed further structural alterations in the postcentral gyrus, posterior cingulate gyrus, and middle temporal gyrus. Familial obesity risk and current obesity/overweight were associated with overlapping and distinct patterns of brain structure alterations. Longitudinal studies are warranted to investigate whether structural changes associated with familial obesity risk predict future weight trajectories.

The Human Breast Milk Metabolome in Overweight and Obese Mothers.

Pre-pregnancy body mass index (BMI) is a major relevance factor, since maternal overweight and obesity can impair the pregnancy outcome and represent risk factors for several neonatal, childhood, and adult conditions, including excessive weight gain, cardiovascular disease, diabetes mellitus, and even behavioral disorders. Currently, breast milk (BM) composition in such category of mothers was not completely defined. In this field, metabolomics represents the ideal technology, able to detect the whole profile of low molecular weight molecules in BM. Limited information is available on human BM metabolites differences in overweight or obese compared to lean mothers. Analyzing all the metabolomics studies published on Medline in English language, this review evaluated the effects that 8 specific types of metabolites found altered by maternal overweight and obesity (nucleotide derivatives, 5-methylthioadenosine, sugar-alcohols, acylcarnitine and amino acids, polyamines, mono-and oligosaccharides, lipids) can exert on the risk of offspring obesity development and other potentially associated health outcomes and complications. However, metabolites variations in samples collected from overweight and obese mothers and the potentially correlated effects highlighted below still need further investigations and should be confirmed in future metabolomics studies on larger samples. Finally, the positive or negative influence of maternal overweight and obesity on the offspring, potentially exerted by breastfeeding, should be analyzed in close correlation with maternal age, genetic and environmental factors, including diet, and taking into account the interactions occurring between BM metabolites and lactobiome. The evaluation of all the factors affecting BM metabolites in overweight and obese mothers can lead to the comprehensive description of such biofluid and the related effects on breastfed subjects, potentially highlighting personalized needs of BM supplementation or short- and long-term prevention strategies to optimize offspring health.

Effect of maternal obesity on neonatal immunity

Abstract Introduction Maternal obesity has been shown to enhance infection, autoimmunity, and allergic sensitization in murine offspring. These data suggest that maternal obesity may be altering the neonatal immune system, but this process has not yet been elucidated. In this study, we are investigating the differences between the immune systems of neonatal mice born to obese versus lean mothers. We are also investigating how maternal obesity influences neonatal immune responses to vaccines since most pediatric vaccines are introduced during the first year of life. Methods Flow cytometry is used to compare splenocyte populations from neonatal offspring of high-fat and control diet parents. Immune responses of neonates to tetanus toxoid conjugated pneumococcal type 14 polysaccharide vaccines (PPS14-TT) are assessed. RNAseq is performed to investigate differences in peritoneal macrophage inflammatory states in neonatal offspring of high-fat and control-diet parents. Results 7-day old neonatal mice from high-fat diet parents have a higher percentage of T cells (CD3+) in the spleen compared to neonates from control-diet parents. The high-fat diet offspring also have an increased B cell (B220+) population. Interestingly, although IgG antibody responses to PPS14-TT vaccine was comparable in the neonates from the two groups, those born to obese mothers developed significantly higher levels of IgM antibodies. Conclusions Data obtained so far suggest that maternal obesity influences the development of the adaptive immune cell populations and alter the antibody responses to vaccines in neonatal offspring. More detailed analysis of neonatal immune responses to vaccines will be presented at the meeting.

The Burden of Placental Histopathology in Stillbirths Associated With Maternal Obesity.

Obesity is an increasing health problem that has become a common medical disorder among women of childbearing age, representing worldwide a risk factor for stillbirth. The aim of the study is to evaluate the association between placental histopathologic findings and obesity in stillbirth. Placentas were analyzed according to the Amsterdam consensus statement. Histologic findings in stillbirth from obese and lean mothers were analyzed and compared with those observed in liveborn controls. Stillbirth in obese mothers displayed placental pathology in all gestational ages, mostly at term of pregnancy. The most observed placental lesions were those consistent with maternal vascular malperfusion of the placental bed. Decidual arteriopathy and placental infarcts appeared specifically associated with maternal obesity. Moreover, obese women with stillbirth showed the highest cumulative number of placental lesions. Considering the significant association between stillbirth, maternal obesity, and placental histopathologic findings, health care providers should be aware about the importance of placental examination in obese women, especially in stillborn cases. The high prevalence of lesions consistent with vascular malperfusion of the placental bed suggests that stillbirth prevention strategies in obese women should rely on the development of tools to study and improve decidual artery functioning early in pregnancy.

Insulin secretory defect may be the major determinant of GDM in lean mothers

AimsTo compare the insulin sensitivity and secretion indices of pregnant Bangladeshi women with GDM and normal glucose tolerance (NGT). MethodsThis cross sectional study was performed with 40 GDM and equal number of NGT pregnant women diagnosed on basis of WHO criterion-2013 during 24–40 weeks of gestation. Glucose was measured by glucose oxidase method and fasting insulin by chemiluminescent immunoassay. Equations of homeostatic model assessment (HOMA) were used to calculate indices of insulin resistance (HOMA-IR), β-cell function (HOMA-B) and insulin sensitivity (HOMA-%S). ResultsThe GDM group had significantly higher insulin resistance as indicated by higher fasting insulin value [GDM vs. NGT; 10.23 (7.94–14.50) vs. 7.07 (5.28–11.07) µIU/ml] and HOMA-IR [GDM vs. NGT; 2.47 (1.75–3.43) vs. 1.50 (0.99–2.22)] and poor β-cell secretion [GDM vs. NGT; HOMA-B: 113.37 (90.30–191.35) vs. 150.98 (109.85–271.72), median (IQR); p < 0.001 for all]. HOMA-B was significantly lower in GDM than NGT with BMI < 23 kg/m2 [GDM vs. NGT; 63.37 (49.19–83.83) vs. 134.89 (93.50–193.17) ng/ml; p = 0.010] despite having statistically comparable difference in IR. BMI was found to be a significant predictor of HOMA-IR in GDM. ConclusionsThough impairments of both insulin secretion and sensitivity are hallmarks in the pathogenesis of GDM, β-cell dysfunction contributes more to development of GDM in those with relatively lower BMI in our population.

Characterizing the Effects of Diabetes and Obesity on Insulin and Leptin Levels amongst Pregnant Women.

In this study, we assess the impact of obesity and diabetes on maternal brain and periphery, as well as fetal exposure to insulin and leptin, and two hormones that play an important role in regulating energy homeostasis. Fasting maternal plasma, fetal cord vein and artery plasma, and maternal cerebrospinal fluid (CSF) were collected in 37 women (12 lean, nondiabetic [prepregnancy body mass index (BMI): 22.9 ± 1.7 kg/m2]; 12 overweight/obese nondiabetic [BMI: 37.8 ± 7.3 kg/m2]; 13 gestational/type 2 diabetes mellitus [BMI: 29.8 ± 7.3 kg/m2]) with uncomplicated singleton pregnancies undergoing elective Cesarean delivery. HbA1C, insulin, glucose, and leptin levels were measured. Compared with lean mothers, mothers with obesity and diabetes mellitus (DM) had significantly lower CSF-to-plasma ratios of insulin. Moreover, mothers with obesity and DM had significantly lower cord arterial and cord venous to maternal plasma ratios of insulin, but not leptin, compared with lean mothers. There were no differences in CSF and cord blood insulin and leptin levels between obese and DM mothers. Compared with lean individuals, mothers with obesity and DM have relative deficiencies in insulin exposure. The patterns observed in mothers with obesity and diabetes were similar highlighting the importance of the maternal metabolic environment in obesity and suggesting obese patients warrant further clinical focus.

Bariatric Surgery Impacts Levels of Serum Lipids during Pregnancy

Introduction: Bariatric surgery confers a high risk for nutritional deficiencies that could affect physiologic adaptation of lipids during pregnancy. We aimed to evaluate differences in serum lipids in pregnant women after bariatric surgery compared to obese and lean mothers. Methods: 25 women with a history of Roux-en-Y gastric bypass (RYGB), 19 obese and 19 normal-weight controls were included at the 24th–28th gestational week for determination of fasting lipids with follow-up in a subgroup after delivery. Data on neonatal biometry were additionally assessed. Results: Women after RYGB showed lower total-cholesterol (TC), low-density lipoprotein C (LDL-C), non-high-density lipoprotein C (non-HDL-C) and triglycerides (TG) compared to obese mothers. Despite their higher BMI, women after RYGB showed lower TC, LDL-C and non-HDL-C than normal-weight mothers. Ultrasensitive C-reactive protein was lower in RYGB mothers than in obese ones, reaching values of lean controls. Differences remained unchanged in BMI-matched comparison. Birth weight percentiles of RYGB offspring were associated with maternal TC (r = 0.59, p = 0.021), LDL-C (r = 0.71, p = 0.003), non-HDL (r = 0.59, p = 0.021) but not HDL-C or TG. After delivery, lipids decreased in all women; however, TC and LDL-C showed more attenuated decline in mothers after RYGB than control women. Conclusion: Pregnancies after RYGB show alterations of physiologic patterns in lipid profile. Further studies are required to evaluate whether imbalances in maternal lipids constitute a risk for abnormal fetal growth in this special cohort.

Association of maternal pre-pregnancy body mass index and pregnancy history with birthweight in offspring

Objective To investigate the association between maternal body mass index (BMI), pregnancy history and birthweight of offspring including low birthweight, macrosomia, small-for-gestational-age (SGA) and large-for-gestational-age (LGA) in Jiashan county of Zhejiang province. Methods We recruited 919 pairs of women and their singleton neonates from the participants of National Free Preconception Health Examination Project (NFPHEP) conducted in Jiashan county of Zhejiang province in 2014 and 2015. Relevant information were extracted from the dataset of NFPHEP. Chi-square test, linear regression, and logistic regression model were applied in statistics analyses. Results Of all the pregnant women, 21.00% (193) were overweight/obesity and 12.73% (117) were lean. For all the neonates, the mean birthweight was 3 339.90 ± 429.98 grams and the number of low birthweight, macrosomia, SGA, and LGA were 28, 57, 48, and 95, respectively. Linear regression analysis indicated that the neonates born to lean mothers had a birthweight of 65.44 (95% confidence interval [95% CI]: – 130.57 – – 0.31) grams lower than that of the neonates born to mothers with normal weight significantly (t = – 1.97, P Conclusion Maternal BMI before pregnancy is associated with the birthweight in offspring. The pre-pregnancy overweight/obese women have an increased risk of to give a birth to a macrosomia and the risk is modified by maternal age, education and pregnancy history of the women.

Effect of Maternal Obesity and Preconceptional Weight Loss on Male and Female Offspring Metabolism and Olfactory Performance in Mice.

According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.

Daily Rhythms Are Altered by High‐Fat Feeding in Female Offspring Born to Obese Mothers

About 20% of women are obese during pregnancy. Children born to obese mothers are at increased risk of obesity, impaired glucose tolerance, and other facets of metabolic syndrome. Disruption of circadian rhythms is also associated with obesity and metabolic dysfunction. Circadian, or daily, rhythms are approximately 24‐hour fluctuations in physiology and behavior. Environmental factors, such as the light‐dark cycle and diet, can alter these rhythms. For example, in male mice, high‐fat diet (HFD) feeding alters daily rhythms and increases body weight. In contrast, female mice fed HFD do not become obese, and their daily rhythms are not altered. Previous studies have shown that female mice will develop diet‐induced obesity if they are born to an obese mother. In this study, we sought to determine if female offspring weaned from obese mothers had disrupted daily rhythms of eating behavior and locomotor activity. Female C57BL/6J mice were fed HFD (60% kcal fat) for 12 weeks (6 weeks prior to pregnancy and throughout pregnancy and nursing). After weaning, female offspring were fed low‐fat diet (LFD, 10% kcal fat) for 5 weeks and then HFD for 8 weeks. We first continuously measured daily eating behavior rhythms with infrared video cameras. All female offspring, regardless of whether the mother was lean or obese, had high‐amplitude rhythms of eating behavior during LFD feeding. Consistent with our previous studies, HFD consumption did not alter the eating behavior rhythms of females born to lean mothers. In contrast, HFD consumption reduced the amplitudes, or robustness, of the eating behavior rhythms in females born to obese mothers. We also investigated the effects of HFD on locomotor activity rhythms, measure by infrared sensors, in female offspring born to lean and obese mothers. The daily rhythms of activity were not affected by HFD feeding in females born to lean mothers. However, the phases (or timing) of the activity rhythms were altered by HFD feeding, compared to LFD feeding, in females born to obese mothers. Together, our results show that maternal obesity causes daily rhythms in female offspring to be susceptible to the effects of HFD feeding.Support or Funding InformationThis study was funded by an American Physiological Society Undergraduate Summer Research Fellowship, the Gertude F. Ribble Trust, and the University of Kentucky.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Nucleic acid cytokine responses in obese children and infants of obese mothers

Almost a third of Irish children are now overweight and the country ranks 58th out of 200 countries for its proportion of overweight youths. With the rising obesity epidemic, and the impaired immune responses of this population, it is vital to understand the effects that obesity has on the immune system and to design future therapeutics, adjuvants and vaccines with overweight and obese populations in mind. Many current vaccines use adjuvants that have been found to be less effective at stimulating the immune response in children compared with adults and there is now substantial effort to design paediatric-focused adjuvants. Additionally, vaccine responses have been shown to be less effective in obese populations indicating that this is a particularly vulnerable population. We have recently identified cytosolic nucleic acids (CNAs), as novel candidate adjuvants for childhood vaccines. Here we investigated whether immune responses to these candidate adjuvants were adversely affected in infants born to overweight or obese mothers, and in overweight and obese children. Type I Interferon (IFN) and proinflammatory cytokines such as Tumor Necrosis Factor α (TNFα) are vital for driving innate and adaptive immune responses. We found that childhood obesity conferred no significant adverse effect on CNA-induced Type I IFN responses when compared with lean children. Similarly, Type I IFN responses were intact in the cord blood of babies delivered from overweight and obese mothers, when compared with lean mothers. There was also no significant impact of obesity on CNA-induced TNFα responses in children or from cord blood of infants born to overweight/obese mothers. In all cases, there was a tendency towards decreased production of innate cytokine Type I Interferon and TNFα, however there was no significant negative correlation. Interestingly, high maternal BMI showed weak and moderate positive correlation with IL-12p70 and IFNγ, respectively, in response to CNA stimulation. This study demonstrates that future adjuvants can be tailored for these populations through the use of activators of CNA sensors.