Alter Weight Gain Research Articles

Isocaloric high-fat diet decreases motivation in the absence of obesity.

Obesogenic diets induce persistent changes in physical activity and motivation. It remains unclear whether these behavioral changes are driven by weight gain or exposure to obesogenic diets themselves. We investigated how exposure to a high-fat diet (HFD) in the absence of obesity affected physical activity, food motivation, and circadian patterns in mice. C57Bl6/J mice were given ~80% of their daily calories in an HFD, known as isocaloric feeding, along with ad libitum access to laboratory chow. Weekly weights, physical activity levels, circadian patterns, operant behavior, and peripheral blood metabolic markers were measured to determine how an isocaloric HFD affected behavior and physiology. Following this period, the same cohort was exposed to an ad libitum HFD to monitor changes in weight gain and physical activity. An isocaloric HFD did not significantly increase weight or change physical activity levels. An isocaloric HFD decreased motivation for sucrose pellets but did not alter weight gain with ad libitum HFD exposure. An isocaloric HFD was associated with decreased motivation for sucrose, as observed in reports of rodent models of obesity. These findings suggest that exposure to an obesogenic diet, even in the absence of significant weight gain, can induce behavioral changes associated with obesity.

Impact of altered gestational weight gain guidelines on midwives in Japan: A cross-sectional study

Objective: In March 2021, modifications were made to the dietary guidelines for expectant and nursing mothers in Japan, resulting in an increased recommended gestational weight gain (GWG) based on the pre-pregnancy body mass index. However, the existing landscape of midwives’ health-guidance practices remains unexplored. This study aimed to elucidate the situation and perceptions of the revised GWG guidelines among midwives in Japan.Methods: This cross-sectional study, conducted between January and March 2023, targeted midwives employed across primary, secondary, and tertiary hospitals in Japan. The participants completed a web-based questionnaire via a QR code and provided responses. Descriptive analysis was employed to discern the midwives’ perceptions of the revised GWG guidelines.Results: A total of 160 midwives (24.2%) completed the web-based questionnaire and were included in the analysis. Of them, 117 (73.1%) knew the recommended GWG had been adjusted. A significant difference was observed in the self-evaluation of health guidance before and after the guideline change (p = .015). While 47.9% of the midwives viewed the guideline change positively, 50.4% considered it neither good nor detrimental. The reasons for this positive perspective included the perceived stringency of previous standards and concerns about the potential effects of strict weight guidance on the physical and mental health of both mothers and children. Those with a neutral stance gave the following reasons: 1) uncertainties about the post-change impact and 2) concerns regarding potential health implications for pregnant women gaining excessive weight.Conclusions: Because not all midwives were aware of the guideline adjustments, the new guidelines must be prioritized.

Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice

ObjectiveThe incidence of gestational diabetes mellitus (GDM) and metabolic disorders during pregnancy are increasing globally. This has resulted in increased use of therapeutic interventions such as metformin to aid in glycemic control during pregnancy. Even though metformin can cross the placental barrier, its impact on offspring brain development remains poorly understood. As metformin promotes AMPK signaling, which plays a key role in axonal growth during development, we hypothesized that it may have an impact on hypothalamic signaling and the formation of neuronal projections in the hypothalamus, the key regulator of energy homeostasis. We further hypothesized that this is dependent on the metabolic and nutritional status of the mother at the time of metformin intervention. Using mouse models of maternal overnutrition, we aimed to assess the effects of metformin exposure on offspring physiology and hypothalamic neuronal circuits during key periods of development. MethodsFemale C57BL/6N mice received either a control diet or a high-fat diet (HFD) during pregnancy and lactation periods. A subset of dams was fed a HFD exclusively during the lactation. Anti-diabetic treatments were given during the first postnatal weeks. Body weights of male and female offspring were monitored daily until weaning. Circulating metabolic factors and molecular changes in the hypothalamus were assessed at postnatal day 16 using ELISA and Western Blot, respectively. Hypothalamic innervation was assessed by immunostaining at postnatal days 16 and 21. ResultsWe identified alterations in weight gain and circulating hormones in male and female offspring induced by anti-diabetic treatment during the early postnatal period, which were critically dependent on the maternal metabolic state. Furthermore, hypothalamic agouti-related peptide (AgRP) and proopiomelanocortin (POMC) neuronal innervation outcomes in response to anti-diabetic treatment were also modulated by maternal metabolic state. We also identified sex-specific changes in hypothalamic AMPK signaling in response to metformin exposure. ConclusionWe demonstrate a unique interaction between anti-diabetic treatment and maternal metabolic state, resulting in sex-specific effects on offspring brain development and physiological outcomes. Overall, based on our findings, no positive effect of metformin intervention was observed in the offspring, despite ameliorating effects on maternal metabolic outcomes. In fact, the metabolic state of the mother drives the most dramatic differences in offspring physiology and metformin had no rescuing effect. Our results therefore highlight the need for a deeper understanding of how maternal metabolic state (excessive weight gain versus stable weight during GDM treatment) affects the developing offspring. Further, these results emphasize that the interventions to treat alterations in maternal metabolism during pregnancy need to be reassessed from the perspective of the offspring physiology.

Altered body weight gain and selected blood constituents of Baluchi lambs fed dried pomegranate peels supplemented ration

Altered body weight gain and selected blood constituents of Baluchi lambs fed dried pomegranate peels supplemented ration

Evaluating different models of maternal stress on stress-responsive systems in prepubertal mice.

Maternal adversity during pregnancy influences neurodevelopment in human and model animal offspring. Adversity can result from stressors coming from many different directions ranging from environmental to nutritional and physiological to immune (e.g., infection). Most stressors result in fetal overexposure to glucocorticoids that have been directly linked to long- and short-term negative impacts on neurological health of offspring. Neuropsychiatric diseases postulated to have fetal origins are diverse and include such things cardiovascular disease, obesity, affective disorders, and metabolic and immune disorders. The experiments in the current study compare 3 stressors: prenatal exposure to dexamethasone (DEX), maternal high fat diet (HFD), and maternal caloric restriction (CR). Offspring of mothers with these treatments were examined prepubertally to evaluate stress responsiveness and stress-related behaviors in in male and female mice. Prenatal exposure to synthetic glucocorticoid, DEX, resulted in decreased neonatal body weights, reduced social interaction behavior, and hypoactive stress response offspring exposed to maternal DEX. Maternal CR resulted in decreased body weights and social interaction behavior in males and females and increased anxiety-like behavior and acute stress response only in males. HFD resulted in altered body weight gain in both sex offspring with decreased anxiety-like behavior in a female-biased manner. The idea that glucocorticoid responses to different stressors might serve as a common stimulus across stress paradigms is insufficient, given that different modes of prenatal stress produced differential effects. Opposite nutritional stressors produced similar outcomes for anxiety-like behavior in both sexes, social-like behavior in females, and a hyperactive adrenal stress response in males. One common theme among the three models of maternal stress (DEX, CR, and HFD) was consistent data showing their role in activating the maternal and fetal immune response. By tuning in on the more immediate immunological aspect on the developing fetus (e.g., hormones, cytokines), additional studies may tease out more direct outcomes of maternal stress in rodents and increase their translational value to human studies.

Reduction in Obesity-Related Hepatic Fibrosis by SR1664.

Peroxisome-proliferator-activated receptor gamma (PPARγ) is a transcription factor with adipogenic, insulin-sensitizing, and antifibrotic properties. Strong PPARγ activators, such as the thiazolidinediones, can induce unwanted effects such as edema, weight gain, and bone loss, and therefore selective modulators of PPARγ are in development. We previously reported that one selective PPARγ modulator, SR1664, reduced toxin-induced hepatic fibrosis and the activation of hepatic stellate cells (HSCs), the main collagen-producing liver cell in fibrosis. In this study, we used a high fat and high carbohydrate (HFHC) model of hepatic steatosis and fibrosis to determine the effect of SR1664. Mice were placed on a standard chow or HFHC diet for 16 weeks, with SR1664 or control treatment for the final 4 weeks. SR1664 did not alter weight gain or fasting insulin or glucose levels. The size of lipid droplets in the HFHC group was reduced by SR1664, but there was no effect on total liver triglyceride levels. The degree of fibrosis was significantly reduced by SR1664 in mice on the HFHC diet, and this was accompanied by a decrease in activated HSC. In summary, SR1664 improved insulin sensitivity and reduced fibrosis in the HFHC diet, suggesting selective PPARγ modulation is effective in obesity-related liver fibrosis.

Dietary delivery of glycomacropeptide within the whey protein matrix is not effective in mitigating tissue ceramide deposition and obesity in mice fed a high-fat diet

Obesity is often accompanied by heightened circulating and tissue inflammation along with an increase in sphingolipids (e.g., ceramides) in metabolically active and insulin-sensitive organs. Whey protein isolate (WPI) has been shown to decrease inflammation and increase insulin sensitivity when given during a high-fat diet (HFD) intervention in rodents. The whey protein bioactive peptide glycomacropeptide (GMP) has also been linked to having anti-inflammatory properties and regulating lipogenesis. Therefore, the purpose of the study was to determine the effect of dietary GMP within the whey protein matrix on tissue inflammation, adiposity, and tissue ceramide accumulation in an obesogenic rodent model. Young adult male mice (10 wk old) underwent a 10-wk 60% HFD intervention. Glycomacropeptide was absent in the control low-fat diet and HFD WPI (-GMP) groups. The HFD WPI (1×GMP) treatment contained a standard amount of GMP, and HFD WPI (2×GMP) had double the amount. We observed no differences in weight gain or reductions in adiposity when comparing the GMP groups to HFD WPI (-GMP). Similarly, insulin resistance and glucose intolerance were not offset with GMP, and skeletal muscle and liver tissue ceramide content was unaltered with the GMP intervention. In contrast, the additional amount of GMP (2×GMP) might adversely affect tissue obesity-related pathologies. Together, dietary GMP given in a whey protein matrix during an HFD intervention does not alter weight gain, insulin resistance, glucose intolerance, and sphingolipid accumulation in the liver and skeletal muscle.

Per- and polyfluoroalkyl substances, gestational weight gain, postpartum weight retention and body composition in the UPSIDE cohort

BackgroundPer- and polyfluoroalkyl substances (PFAS) are synthetic chemicals found in drinking water and consumer products, resulting in ubiquitous human exposure. PFAS have been linked to endocrine disruption and altered weight gain across the lifespan. A limited and inconsistent body of research suggests PFAS may impact gestational weight gain (GWG) and postpartum body mass index (BMI), which are important predictors of overall infant and maternal health, respectively.MethodsIn the Understanding Pregnancy Signals and Infant Development (UPSIDE/UPSIDE-MOMs) study (n = 243; Rochester, NY), we examined second trimester serum PFAS (PFOS: perfluorooctanesulfonic acid, PFOA: perfluorooctanoic acid, PFNA: perfluorononanoic acid, PFHxS: perfluorohexanesulfonic acid, PFDA: perfluorodecanoic acid) in relation to GWG (kg, and weekly rate of gain) and in the postpartum, weight retention (PPWR (kg) and total body fat percentage (measured by bioelectrical impedance)). We fit multivariable linear regression models examining these outcomes in relation to log-transformed PFAS in the whole cohort as well as stratified by maternal pre-pregnancy BMI (< 25 vs. = > 25 kg/m2), adjusting for demographics and lifestyle factors. We used weighted quantile sum regression to find the combined influence of the 5 PFAS on GWG, PPWR, and body fat percentage.ResultsPFOA and PFHxS were inversely associated with total GWG (PFOA: ß = -1.54 kg, 95%CI: -2.79, -0.30; rate ß = -0.05 kg/week, 95%CI: -0.09, -0.01; PFHxS: ß = -1.59 kg, 95%CI: -3.39, 0.21; rate ß = -0.05 kg/week, 95%CI: -0.11, 0.01) and PPWR at 6 and 12 months (PFOA 6 months: ß = -2.39 kg, 95%CI: -4.17, -0.61; 12 months: ß = -4.02 kg, 95%CI: -6.58, -1.46; PFHxS 6 months: ß = -2.94 kg, 95%CI: -5.52, -0.35; 12 months: ß = -5.13 kg, 95%CI: -8.34, -1.93). PFOA was additionally associated with lower body fat percentage at 6 and 12 months (ß = -1.75, 95%CI: -3.17, -0.32; ß = -1.64, 95%CI: -3.43, 0.16, respectively) with stronger associations observed in participants with higher pre-pregnancy BMI. The PFAS mixture was inversely associated with weight retention at 12 months (ß = -2.030, 95%CI: -3.486, -0.573) amongst all participants.ConclusionPFAS, in particular PFOA and PFHxS, in pregnancy are associated with altered patterns of GWG and postpartum adiposity with potential implications for fetal development and long-term maternal cardiometabolic health.

Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity.

Obesity is a complex medical condition that is linked to various health complications such as infertility, stroke, and osteoarthritis. Understanding the neurobiology of obesity is crucial for responding to the etiology of this disease. The hypothalamus coordinates many integral activities such as hormone regulation and feed intake and numerous studies have observed altered hypothalamic gene regulation in obesity models. Previously, it was reported that the promoter region of the satiety gene, Pomc, has increased DNA methylation in the hypothalamus following short-term exposure to a high fat diet, suggesting that epigenetic-mediated repression of hypothalamic Pomc might contribute to the development of obesity. However, due to technical limitations, this has never been directly tested. Here, we used the CRISPR-dCas9-TET1 and dCas9-DNMT3a systems to test the role of Pomc DNA methylation in the hypothalamus in abnormal weight gain following acute exposure to a high fat diet in male rats. We found that exposure to a high fat diet increases Pomc DNA methylation and reduces gene expression in the hypothalamus. Despite this, we found that CRISPR-dCas9-TET1-mediated demethylation of Pomc was not sufficient to prevent abnormal weight gain following exposure to a high fat diet. Furthermore, CRISPR-dCas9-DNMT3a-mediated methylation of Pomc did not alter weight gain following exposure to standard or high fat diets. Collectively, these results suggest that high fat diet induced changes in Pomc DNA methylation are a consequence of, but do not directly contribute to, abnormal weight gain during the development of obesity.

Maternal exposure to phthalates and total gestational weight gain in the LIFECODES birth cohort.

Excessive gestational weight gain contributes to adverse maternal and neonatal outcomes. Environmental exposures such as phthalates may lead to metabolic dysregulation, and studies suggest possible associations between maternal phthalate exposure and altered gestational weight gain. We assessed the association between nine maternal phthalate metabolites and measures of total gestational weight gain (pre-pregnancy to median 35.1 weeks of gestation) in a case-control study nested within LIFECODES (N=379), a prospective birth cohort from Boston, Massachusetts (2006-2008). Our primary outcome was total gestational weight gain z score, a measure independent of gestational age that can provide a less biased estimate of this association. Our secondary outcomes were total gestational weight gain, rate of gestational weight gain, and adequacy ratio. The results were stratified by pre-pregnancy body mass index category. We found that concentrations of mono-(3-carboxypropyl) phthalate (MCPP) and mono-n-butyl phthalate (MBP) were positively associated with total gestational weight gain z scores among participants with obesity: adjusted mean difference (95% Confidence Interval [CI]) =0.242 (0.030 - 0.455) and 0.105 (-0.002 - 0.212) corresponding to an excess weight gain of 1.81kg and 0.77kg at 35 weeks of gestation per interquartile range-increase in MCPP and MBP, respectively. Also, among participants with obesity, MBP demonstrated a potential non-linear relationship with gestational weight gain in cubic spline models. These findings suggest that phthalates may be related to higher gestational weight gain, specifically, among individuals with pre-pregnancy obesity. Future research should investigate whether pregnant people with obesity represent a subpopulation with sensitivity to phthalate exposures.

Evaluation of acute toxicity, 28-day repeated dose toxicity, and genotoxicity of Moringa oleifera leaves infusion and powder

Ethnopharmacological relevanceMoringa oleifera Lam. leaves infusion and powder are widely used by population due the nutritional and medicinal potentials, however data regarding safety of use are still inconclusive, leading to prohibition of this plant in some countries. Aim of the studyThe present work investigated the nutritional and phytochemical composition, acute and 28-day repeated dose toxicity, and genotoxicity of M. oleifera leaves infusion and powder. Materials and methodsFor nutritional characterization of leaf powder, it was determined: humidity; mineral residue (ash); total lipid, protein, carbohydrate, and crude fiber contents; and total caloric value. Phytochemical composition was determined by high performance liquid chromatography (HPLC). The acute toxicity assay used Swiss female albino mice and oral administration in a single dose at 2000 and 5000 mg/kg of infusion or powder. The 28-day repeated dose toxicity assay employed female and male mice, with oral administration of infusion or powder at the doses 250, 500 and 1000 mg/kg. The animals were evaluated for body weight, water and feed consumption, biochemical and hematological parameters, and histology of the liver, spleen, and kidneys. In vivo genotoxicity and mutagenicity (2000 mg/kg) were evaluated by the comet assay and the micronucleus test, respectively. ResultsNutritional characterization confirmed that M. oleifera leaves are rich in proteins, carbohydrates, lipids, minerals, and fiber. HPLC indicated the presence of flavonoids and cinnamic derivatives as major polyphenols. Acute toxicity did not reveal alterations in weight gain and water and feed consumptions and no change in biochemical, hematological, and histological parameters. Behavior alterations was observed in the first 2 h after administration at 5000 mg/kg in both treatments. Infusion did not present toxicity when administered for 28 days. Conversely, the powder at 500 and 1000 mg/kg promoted liver and kidney damages observed through biochemical parameters and histopathology. Genotoxicity and mutagenicity were not detected at 2000 mg/kg. ConclusionsThe present study reveals that M. oleifera leaves are an important source of polyphenols and nutrients. Indiscriminate use of both infusion and crude leaf powder above 2000 mg/kg and powder at 500 and 1000 mg/kg are not recommended. Chronic toxicological studies and establishment of preparation protocols are suggested aiming to guarantee the safety in the use of M. oleifera leaves as nutraceutical by population.

307-OR: Impaired Differentiation of Trpv1-Positive Adipose Progenitors Activates Compensatory Thermogenic Mechanisms

Brown and beige thermogenic adipocytes are specialized in energy consumption and linked to metabolic health. Canonically, thermogenic adipocytes are thought to be derived from mesenchymal PdgfRα+ adipocyte progenitor cells (APC) . We recently identified a novel population of cold-recruited APCs from the vascular smooth muscle lineage marked by the expression of the ion channel Trpv1 in mouse adipose tissue. To determine the function of the Trpv1+ APC-derived adipocytes, we impaired their adipogenic capacity by deletion of Pparγ in Trpv1-expressing cells in mice (Trpv1-Cre::Pparγ-flox) . Inhibition of de novo adipogenesis from Trpv1+ APCs resulted in modest changes in brown adipose tissue, but it caused a marked reduction in the expression of cold-induced browning genes, including UCP1, in white adipose tissue (WAT) , indicating impaired beige adipogenesis. Interestingly, Trpv1-Cre::Pparγ-flox mice did not show altered weight gain, glucose tolerance, or insulin sensitivity on either regular chow or high-fat diets. This discrepancy led us to search for potential compensatory mechanisms. We observed increased PdgfRα expression in WAT of Trpv1-Cre::Pparγ-flox animals, suggesting that impaired adipogenic capacity of the Trpv1+ APCs may trigger recruitment of the PdgfRα+ APCs. Additionally, while UCP1 expression was noticeably reduced in the beige adipocytes within WAT, the expression of transcripts involved in the UCP1-independent thermogenic pathways, including Ckmt1, Gatm, and Slc6a8, key components of the creatine futile cycle, was increased in the WAT of the Trpv1-Cre::Pparγ-flox mice upon cold exposure. Together, these data highlight a potential distinction between the thermogenic pathways mediated by adipocytes derived from the Trpv1+ versus those derived from the PdgfRα+ APCs. This functional difference of thermogenic adipocytes could be critical in designing strategies to target these cells as a therapeutic approach for metabolic diseases. Disclosure H.Camara: None. F.Shamsi: None. M.Lynes: None. Y.Tseng: Consultant; Cellarity. Funding National Institutes of Health (R01DK102898)

Modulating expression of a BTB-ZF transcription factor in adipose resident NKT cells alters function and disrupts metabolism regulation.

Abstract Natural killer T cells (NKTs) are potent modulators of the immune system that can regulate the function of other cell types largely through their rapid and robust production of a wide variety of cytokines. One tissue that relies on the interactions of NKT cells with various cell types is white adipose tissue. Adipose resident NKT cells (arNKTs) maintain tissue homeostasis and metabolism through anti-inflammatory interactions such as modulating macrophage functions and enhancing the proliferation and function of FoxP3-expressing Tregs. However, arNKTs are phenotypically distinct from other populations of NKT cells in their transcription factor expression. We have found that genetically modulating the expression of a BTB-ZF transcription factor in NKT cells alters the frequency and function of arNKTs, thereby altering weight gain and metabolic function. Our data show that sustained expression of the BTB-ZF transcription factor in arNKT cells leads to lower arNKT frequency, altered function, and enhanced weight gain in a model of obesity (60% high fat diet). While deletion of the transcription factor during NKT cell development leads to lower arNKT frequency, altered arNKT phenotype, and impaired weight gain when fed 60% high fat diet. Collectively, our data show that dynamic changes in the expression of a BTB-zinc finger transcription factor during NKT cell development and tissue-homing are required for normal arNKT cell function, and preservation of adipose tissue metabolism. Our findings imply that NKT cell inability to temporally regulate the expression of a single transcription factor may drive adipose tissue dysregulation and metabolic disease. Supported by NIH/NIAID R21 AI159066-01

Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet.

Simple SummaryThe nuclear protein Krüppel-like factor 9 (KLF9) suppresses development of cancers in multiple tissues including the liver. However, a mechanistic basis for how KLF9 decreases cancer initiation/development has not been elucidated. Here, we used a mouse model in which the Klf9 gene was ablated and placed wild-type and mutant animals of both sexes on a high-fat, obesogenic diet. We then examined how the presence or absence of KLF9 affected adiposity, as well as indices of liver oxidative stress and inflammation, and systemic oxidative stress. Results demonstrate that KLF9 is a suppressor of liver oxidative stress and inflammation which may underlie its tumor suppressive actions in liver and other tissues.Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9+/+ (wild type, WT) and Klf9−/− (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9−/− mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9−/− mice of both sexes had increased liver weight/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9−/− mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9−/− mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues.

Prenatal exposures to mixtures of endocrine disrupting chemicals and children\u2019s weight trajectory up to age 5.5 in the SELMA study

Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child’s weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI − 0.16, − 0.06), slower infant growth spurt rate of 0.01 (95% CI − 0.03, − 0.01, on the log10 scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.

Effects of Peripartal Sertraline on Maternal Calcium Metabolism and Maternal Bone Health

Abstract Lactation taxes mothers’ bone health, causing them to lose up to 10% of their bone mass for milk calcium. Selective serotonin reuptake inhibitor antidepressants (SSRIs) are commonly used during pregnancy and lactation but independently decrease bone mass. We previously demonstrated that both maternal and offspring bone densities were compromised by maternal treatment with the SSRI fluoxetine throughout pregnancy and lactation. In this study, we examined whether sertraline similarly affect maternal and offspring bone. Female C57BL/6 dams (n=23/group) were treated with sertraline (10 mg/kg/d) or a vehicle (DMSO) for 41 d (E0-lactation(L) 21). Pups were euthanized at weaning (L21). Dams were euthanized at peak lactation (L10, n=4/group), weaning (L21, n=9/group) or 3 mo post-weaning (n=10/group) for analysis. Sertraline treatment did not affect dams’ weight gain during pregnancy or lactation and did not impact milk production/consumption, measured by weigh-suckle-weigh. Unlike fluoxetine, which increases circulating calcium, sertraline treatment reduced serum calcium concentration at L21 compared with control (p&amp;lt;0.05). Mammary calcium genes were not altered at L10, but at L21 we observed decreased mammary expression of the calcium transporters Orai1, Spca1, Spca2, and Serca2 (p&amp;lt;0.05), and a tendency for decreased Pthlh (a calcium-regulating peptide; p=0.08). In the intestinal duodenum, Calb1 (a cytosolic calcium trafficking protein) expression was increased at L10 and L21 (p&amp;lt;0.05), and the calcium transporters Trpv6, Pmca1 and Spca2 were increased by L21 (p&amp;lt;0.05). Sertraline treatment did not affect L21 calcium concentration in either tissue, although the mammary gland calcium was 3.5 times that of the duodenum. Previously, we reported that circulating markers of bone formation (P1NP) or bone resorption (CTX) were unchanged in sertraline-treated dams at L21. This is unlike fluoxetine, which decreased P1NP without altering CTX. Furthermore, compared with control, sertraline treatment did not alter expression of bone resorption or formation genes (e.g. Trap, Rank/RankL, Alp, Runx2) in maternal femoral bone at L21 or 3 mo post-weaning. Interestingly, in utero exposure to sertraline reduced litter size (5.4 vs 6.8 pups/dam, p&amp;lt;0.01) and increased pup mortality (20% vs 5% dead pups/litter, p&amp;lt;0.01) during the first 24 hours postpartum compared with controls, but did not affect length of gestation or live birth rate. Exposure to sertraline during lactation did not alter weight gain in the surviving offspring, nor did it alter circulating calcium in the pups at weaning, suggesting an adequate supply of calcium in the milk from the dam. These data suggest that, compared with high-dose fluoxetine, low-dose peripartal sertraline has a milder impact on maternal bone and may reduce mammary calcium but could induce a failure to thrive in the offspring.

Betamethasone as a potential treatment for preterm birth associated with sterile intra-amniotic inflammation: a murine study

Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmin-induced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic inflammation in mice. Under ultrasound guidance, the first cohort of dams received an intra-amniotic injection of the alarmin high-mobility group box-1 (HMGB1, n=10) or phosphate-buffered saline (PBS, n=9) as controls. A second cohort of dams received HMGB1 intra-amniotically and were subcutaneously treated with betamethasone (n=15) or vehicle (n=15). Dams were observed until delivery, and perinatal outcomes were observed. Intra-amniotic HMGB1 reduced gestational length (p=0.04), inducing preterm birth in 40% (4/10) of cases, of which 100% (4/4) were categorized as late preterm births. Importantly, treatment with betamethasone extended the gestational length (p=0.02), thereby reducing the rate of preterm birth by 26.6% (from 33.3% [5/15] to 6.7% [1/15]). Treatment with betamethasone did not worsen the rate of neonatal mortality induced by HMGB1 or alter weight gain in the first three weeks of life. Treatment with betamethasone prevents preterm birth induced by the alarmin HMGB1. This study supports the potential utility of betamethasone for treating women with sterile intra-amniotic inflammation.

Effects of consumption of acerola, cashew and guava by-products on adiposity and redox homeostasis of adipose tissue in obese rats

Fruit by-products contain phytochemicals, fibers and other components that can improve the redox imbalance of obesity. The objective was to evaluate the effects of consumption of by-products of acerola, cashew and guava on the adiposity and redox homeostasis of adipose tissue in obese rats. The animals were separated into 5 groups, control (CTL), high fat (HF), HF supplemented with acerola (HFA), cashew (HFC) and guava (HFG). Thiol quantification, lipid profile, catalase (CAT) and glutathione peroxidase (GPX) test were performed. TGL and VLDL levels were increased in HF group, and the treated groups did not change the lipid profile. CAT activity was increased in HFA and HFG groups. HFA was able to reduce the weight of the subcutaneous cushion. Treatment with fruit by-products did not alter weight gain, energy efficiency and body weight. Thus, the by-products of acerola and guava can be used as a sustainable alternative in the treatment of obesity.

DIETARY MANNAN-OLIGOSACCHARIDE INCREASES REACTIVE OXIGEN SPECIES PRODUCTION BUT DECREASES SERUM LYSOZYME IN HIGH LEVELS OF INCLUSION FOR NILE TILAPIA

In the present experiment, the effects of mannan-oligosaccharide (MOS) on health and growth of Nile tilapia juveniles were investigated. In addition to the control treatment (without MOS),three levels of MOS were included in Nile tilapia diets (1, 8, and 15 g kgâˆ"™1), and hematology, reactive oxygen species (ROS) production, lysozyme and productive parameters were analyzed. Fish blood was sampled at day zero (basal sample) and after 60 days of trial, and the productive parameters were evaluated at the end of the experiment. MOS feeding decreased the feed consumption (p = 0.0299) in fish fed with 1 and 8 g kg-1, but without any alteration in weight gain (WG) and feed conversion ratio (FCR). No changes were observed in the hematology due to MOS feeding after 60 days. However, the prebiotic caused changes in the innate immunity of fish, giving rise to ROS production in fish fed with 1 g kg-1 (p&lt;0.0001) and decreasing the serum lysozyme activity of fish fed with 15 g kg-1 (p&lt;0.0001). In conclusion, the authors recommend the inclusion of 1 g kg-1 for Nile tilapia juveniles feeding due to the positive effect in innate immune system.

Assessing the safety of using the dry extract of Justicia pectoralis Jacq. (Acanthaceae) during pregnancy of Wistar rats

Ethnopharmacological relevanceJusticia pectoralis Jacq. (Acanthaceae), popularly known as tilo, chambá and anador, is widely used in folk medicine in Latin American countries as a sedative, anti-anxiety, reducing menopause symptoms and in the treatment of pathologies of the respiratory tract. Although J. pectoralis is widely used by the female population, there are no studies on the safety of using this species during pregnancy. Aim of this studyTo evaluate the effects of prenatal treatment with dry extract from the aerial parts of J. pectoralis on maternal and developmental toxicity in Wistar rats. Material and methodsPregnant Wistar rats (n = 10/group) were treated from gestational day (GD) 0–20 with the vehicle (control group) or with the dry extract of J. pectoralis at doses of 300, 600 or 1200 mg/kg. During pregnancy, clinical signs of toxicity, maternal weight, feed and water intake were evaluated. On GD 21, rats were anesthetized and intracardiac blood was collected to evaluate biochemical parameters. During cesarean section, reproductive performance parameters were recorded. The liver, kidneys, uterus and ovaries were removed for histopathological analysis. Fetuses were examined for possible malformations and/or skeletal and visceral variations. ResultsTreatment with dry extract of J. pectoralis did not alter weight gain, feed intake or biochemical and maternal reproductive performance parameters There were also no significant histopathological changes in the maternal organs, as well as external, skeletal and visceral malformations in the fetuses. ConclusionOral administration of J. pectoralis dry extract during pregnancy did not induce maternal toxicity or embryotoxic and teratogenic effects.