Skeletal Muscle Lipid Metabolism and Markers of Insulin Resistance in Young Male Low Birth Weight Offspring in Combination With a Postnatal Western Diet

Low birth weight offspring are at increased risk for developing metabolic syndrome in later life, specifically its precursor, insulin resistance (IR). Reduced mitochondrial lipid metabolism is implicated in IR pathogenesis, promoting accumulation of acylcarnitines, and potentiating alterations in phosphorylation status of insulin signaling intermediates. While high-energy Western diets are classically implicated in IR progression, the in utero environment was recently highlighted as a major programming mechanism of later life IR. Using a guinea pig model of placental insufficiency, we investigated how an adverse in utero environment impacts later life mitochondrial lipid metabolism and IR progression, as well as its interaction with a postnatal Western diet. Markers of mitochondrial dysfunction and reduced lipid metabolism, including acylcarnitine accumulation, were observed in conjunction with disrupted phosphorylation of insulin signaling intermediates in skeletal muscle of low birth weight offspring. Additionally, a postnatal Western diet unmasked low birth weight-induced mitochondrial dysfunctions, promoting further acylcarnitine accumulation

Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency

Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs.

BACKGROUND: The gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse METHODS: The fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed. RESULTS: The life-long consumption of WD following weaning into young adulthood resulted in increased total cholesterol, triglycerides and alanine aminotransferase levels in association with an altered GIT microbiota when compared to offspring consuming CD. Neither birth weight nor sex were associated with any significant changes in microbiota alpha diversity, by measuring the Shannon\u27s diversity index. One hundred forty-eight operational taxonomic units were statistically distinct between the diet groups, independent of birth weight. In the WD group, significant decreases were detected in DISCUSSION: These results describe the GIT microbiota in a guinea pig model of LBW and WD associated metabolic syndrome and highlight several WD specific GIT alterations associated with human metabolic disease

Differential and synergistic effects of low birth weight and western diet on skeletal muscle vasculature, mitochondrial lipid metabolism and insulin signaling in male guinea pigs

Low birth weight (LBW) offspring are at increased risk for developing insulin resistance, a key precursor in metabolic syndrome and type 2 diabetes mellitus. Altered skeletal muscle vasculature, extracellular matrix, amino acid and mitochondrial lipid metabolism, and insulin signaling are implicated in this pathogenesis. Using uteroplacental insufficiency (UPI) to induce intrauterine growth restriction (IUGR) and LBW in the guinea pig, we investigated the relationship between UPI-induced IUGR/LBW and later life skeletal muscle arteriole density, fibrosis, amino acid and mitochondrial lipid metabolism, markers of insulin signaling and glucose uptake, and how a postnatal high-fat, high-sugar “Western” diet (WD) modulates these changes. Muscle of 145-day-old male LBW glucose-tolerant offspring displayed diminished vessel density and altered acylcarnitine levels. Disrupted muscle insulin signaling despite maintained whole-body glucose homeostasis also occurred in both LBW and WD-fed male “lean” offspring. Additionally, postnatal WD unmasked LBW-induced impairment of mitochondrial lipid metabolism, as reflected by increased acylcarnitine accumulation. This study provides evidence that early markers of skeletal muscle metabolic dysfunction appear to be influenced by the in utero environment and interact with a high-fat/high-sugar postnatal environment to exacerbate altered mitochondrial lipid metabolism, promoting mitochondrial overload

Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency

Impact of birth weight and postnatal diet on the gut microbiota of young adult guinea pigs

Background. The gastrointestinal tract (GIT) microbiota is essential to metabolic health, and the prevalence of the Western diet (WD) high in fat and sugar is increasing, with evidence highlighting a negative interaction between the GIT and WD, resulting in liver dysfunction. Additionally, an adverse in utero environment such as placental insufficiency resulting in low birth weight (LBW) offspring, contributes to an increased risk of metabolic diseases such as fatty liver infiltration and liver dysfunction in later life. We sought to understand the potential interactive effects of exposure to a WD upon growing LBW offspring. We postulated that LBW offspring when challenged with a poor postnatal diet, would display an altered microbiota and more severe liver metabolic dysfunction. Methods. The fecal microbiota of normal birth weight (NBW) and LBW young guinea pig offspring, weaned onto either a control diet (CD) or WD was determined with 16S rRNA gene next generation sequencing at young adulthood following the early rapid growth phase after weaning. A liver blood chemistry profile was also performed. Results. The life-long consumption of WD following weaning into young adulthood resulted in increased total cholesterol, triglycerides and alanine aminotransferase levels in association with an altered GIT microbiota when compared to offspring consuming CD. Neither birth weight nor sex were associated with any significant changes in microbiota alpha diversity, by measuring the Shannon\u27s diversity index. One hundred forty-eight operational taxonomic units were statistically distinct between the diet groups, independent of birth weight. In the WD group, significant decreases were detected in Barnesiella, Methanobrevibacter smithii and relatives of Oscillospira guillermondii, while Butyricimonas and Bacteroides spp. were increased. Discussion. These results describe the GIT microbiota in a guinea pig model of LBW and WD associated metabolic syndrome and highlight several WD specific GIT alterations associated with human metabolic disease

The virtual reality classroom: a randomized control trial of medical student knowledge of postpartum hemorrhage emergency management

Objective: To investigate the use of a virtual reality learning environment (VRLE) to enhance medical student knowledge of postpartum hemorrhage (PPH) emergency management and insertion of a postpartum balloon. Methods: A randomized control trial involving medical students from University College Dublin, Ireland. Participants were randomly allocated to the intervention group (VRLE tutorial) or control group (PowerPoint tutorial on the same topic). All participants completed pre-learning experience and post-learning experience surveys. Both groups were timed and assessed on postpartum balloon insertion technique on a model pelvis. The primary outcome was assessment of student knowledge. Secondary outcomes included confidence levels, time taken to complete the task, technique assessment, satisfaction with the learning environment, and side effects of VR. Results: Both learning experiences significantly (p p = 0.039). Both learning experiences significantly (p Conclusion: Receiving formal instruction, regardless of format, enhances students' knowledge and confidence of the topic covered. Students who received instruction via the VRLE assembled the postpartum balloon faster than students who received didactic teaching. VR may be beneficial in teaching hands-on procedural skills in obstetrics and gynecology education.</p

Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency

Global impact of the first coronavirus disease 2019 (COVID-19) pandemic wave on vascular services

This online structured survey has demonstrated the global impact of the COVID-19 pandemic on vascular services. The majority of centres have documented marked reductions in operating and services provided to vascular patients. In the months during recovery from the resource restrictions imposed during the pandemic peaks, there will be a significant vascular disease burden awaiting surgeons. One of the most affected specialtie