Publications by authors named "Kartik Shankar"

Background: Per- and polyfluoroalkyl substances (PFAS) are environmental toxicants associated with adverse neonatal outcomes. The exact mechanisms by which PFAS impairs neonatal health are undefined, but the placenta is a likely target.

Objective: We applied a systems biology approach to identify placental RNA co-expression modules (gene sets) associated with PFAS exposure and birth weight.

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Placental gestational age acceleration (GAA) is the difference between the actual gestational age (GA) at birth and their estimated epigenetic gestational age (EGA), which is calculated from placental DNA methylation. Understanding the role of placental GAA in postnatal growth trajectories is crucial for early identification of infants at risk of altered growth patterns and associated long-term health outcomes. The objective of this study is to investigate the association between placental GAA and longitudinal growth trajectories specifically weight, height, fat mass, and lean mass gain in early childhood.

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Background: Per- and polyfluoroalkyl substances (PFAS) are environmental toxicants associated with adverse neonatal outcomes. The exact mechanisms by which PFAS impairs neonatal health are undefined, but the placenta is a likely target.

Objective: We applied a systems biology approach to identify placental RNA co-expression modules (gene sets) associated with PFAS exposure and birth weight.

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Maternal weight and diet before and during pregnancy have a substantial impact on offspring metabolic health, though sex-specific differences in metabolic and adipose tissue adaptations to maternal overnutrition remain insufficiently understood. Using a mouse model of maternal high-fat (HF) diet-induced obesity, this study assessed the sexually dimorphic responses on offspring adiposity, physiology, and adipose tissue function. Male offspring of HF diet-fed dams exhibited greater weight gain and adiposity, impaired glucose homeostasis, elevated serum levels of insulin, leptin, and cholesterol, along with increased adipogenic and heat shock proteins (HSPs) gene expression in white adipose tissue compared to female offspring.

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Background: Undernutrition in females of childbearing age increases risk of fetal growth restriction and poor infant development. A rise in ambient temperature is thought to exacerbate the effects of undernutrition. However, few mechanistic studies exist to examine the interactions between maternal nutritional status and ambient temperature on fetal growth.

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Introduction: Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals and widespread environmental contaminants. PFAS cross the placental barrier and reach the developing fetus with potential impacts on many organ systems. There are no studies of PFAS in residents of central Arkansas despite reports of environmental contamination in the region.

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High cardiorespiratory fitness and exercise show evidence of altering bile acid (BA) metabolism and are known to protect or treat diet-induced hepatic steatosis, respectively. Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of 2H2O. We also leveraged mice with inducible liver-specific deletion of Cyp7a1 (LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis.

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Background: Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that may impact placental function, and potentially gestational age acceleration (GAA), a deviation from reported and predicted gestational age. GAA potentially represents differences in cell maturation in response to a challenging environment.

Objective: This study aimed to characterize the effects of individual and mixtures of PFAS on GAA, cell composition, birth length, and birthweight.

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The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas (N = 151).

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Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited.

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Background: The carbon isotope ratio (CIR) is a candidate biomarker for sugar-sweetened beverage (SSB) intake in the United States. However, research specific to youth, who differ in their physiology and dietary patterns compared with adults, is lacking.

Objectives: We evaluated longitudinal associations of SSB intakes across childhood/adolescence with serum CIR.

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Background: Low birth weight (LBW; <2,500 g) affects approximately 15 to 20 percent of global births annually and is associated with suboptimal child development. Recent studies suggest a link between the maternal gut microbiome and poor obstetric and perinatal outcomes. The goal of this study was to examine relationships between maternal microbial taxa, fecal metabolites, and maternal anthropometry on incidence of LBW in resource-limited settings.

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Background: Maternal undernutrition is the most common cause of fetal growth restriction (FGR) worldwide. FGR increases morbidity and mortality during infancy, as well as contributes to adult-onset diseases including obesity and type 2 diabetes. The role of the maternal or offspring microbiome in growth outcomes following FGR is not well understood.

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Background: Pre-pregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, the impact of pre-pregnancy overweight on immune cell gene expression during pregnancy and its association with maternal and infant outcomes is not well explored.

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Background/aim: This study examined the effects of tocotrienols (TT) in conjunction with statin on glucose homeostasis, bone microstructure, gut microbiome, and systemic and liver inflammatory markers in obese C57BL/6J mice.

Materials And Methods: Forty male C57BL/6J mice were fed a high-fat diet (HFD) and assigned into four groups in a 2 (no statin vs. 120 mg statin/kg diet)×2 (no TT vs.

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The placenta is crucial for fetal development, is affected by PFAS toxicity, and evidence is accumulating that gestational PFAS perturb the epigenetic activity of the placenta. Gestational PFAS exposure is can adversely affect offspring, yet individual and cumulative impacts of PFAS on the placental epigenome remain underexplored. Here, we conducted an epigenome-wide association study (EWAS) to examine the relationships between placental PFAS levels and DNA methylation in a cohort of mother-infant dyads in Arkansas.

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Background And Aims: Spinal cord injury (SCI) affects roughly 300,000 Americans with 17,000 new cases added annually. In addition to paralysis, 60% of people with SCI develop neurogenic bowel (NB), a syndrome characterized by slow colonic transit, constipation, and chronic abdominal pain. The knowledge gap surrounding NB mechanisms after SCI means that interventions are primarily symptom-focused and largely ineffective.

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Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX).

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Background: Human milk oligosaccharides have been shown to relate to the infant gut microbiome. However, the impact of other human milk components on infant gut bacterial colonization remains unexplored.

Objectives: Our cross-sectional analysis aimed to investigate associations between human milk components (energy, macronutrients, free amino acids, inflammatory markers, and hormones) and infant gut microbiome diversity and composition (phylum, family, and genus) at 6 mo of age.

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Objective: Menopause adversely impacts systemic energy metabolism and increases the risk of metabolic disease(s) including hepatic steatosis, but the mechanisms are largely unknown. Dosing female mice with vinyl cyclohexene dioxide (VCD) selectively causes follicular atresia in ovaries, leading to a murine menopause-like phenotype.

Methods: In this study, we treated female C57BL6/J mice with VCD (160 mg/kg i.

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Menopause adversely impacts systemic energy metabolism and increases the risk of metabolic disease(s) including hepatic steatosis, but the mechanisms are largely unknown. Dosing female mice with vinyl cyclohexene dioxide (VCD) selectively causes follicular atresia in ovaries, leading to a murine menopause-like phenotype. In this study, we treated female C57BL6/J mice with VCD (160mg/kg i.

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While exercise (EX) during pregnancy is beneficial for both mother and child, little is known about the mechanisms by which maternal exercise mediates changes in utero. Six-week-old female C57BL/6 mice were divided into two groups: with (exercise, EX; N = 7) or without (sedentary, SED; N = 8) access to voluntary running wheels. EX was provided via 24 h access to wheels for 10 weeks prior to conception until late pregnancy (18.

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Background: Infant feeding patterns have been linked with obesity risk in childhood, but associations with precise measures of body fat distribution are unclear.

Objective: We examined associations of infant feeding practices with abdominal fat and hepatic fat trajectories in childhood.

Methods: This study included 356 children in the Healthy Start Study, a prospective prebirth cohort in Colorado.

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Background: Fetal growth restriction (FGR) increases risk for development of obesity and type 2 diabetes. Using a mouse model of FGR, we tested whether metabolic outcomes were exacerbated by high-fat diet challenge or associated with fecal microbial taxa.

Methods: FGR was induced by maternal calorie restriction from gestation day 9 to 19.

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Men are diagnosed with type 2 diabetes at lower body mass indexes than women; the role of skeletal muscle in this sex difference is poorly understood. Type 2 diabetes impacts skeletal muscle, particularly in females who demonstrate a lower oxidative capacity compared to males. To address mechanistic differences underlying this sex disparity, we investigated skeletal muscle mitochondrial respiration in female and male rats in response to chronic high-fat, high-sugar (HFHS) diet consumption.

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