Mitochondria are key regulators of metabolism and ATP supply in skeletal muscle, while circadian rhythms influence many physiological processes. However, whether mitochondrial function is intrinsically regulated in a circadian manner in mouse skeletal muscle is inadequately understood. Accordingly, we measured post-absorptive transcript abundance of markers of mitochondrial biogenesis, dynamics, and metabolism (extensor digitorum longus [EDL], soleus, gastrocnemius), protein abundance of electron transport chain complexes (EDL and soleus), enzymatic activity of SDH (tibialis anterior and plantaris), and maximum uncoupled respiration (tibialis anterior) in different skeletal muscles from female C57BL/6NJ mice at four zeitgeber times (ZT), ZT 1, 7, 13, and 19.
View Article and Find Full Text PDFIntroduction: People with idiopathic pulmonary fibrosis (IPF) and other forms of progressive pulmonary fibrosis (PPF) have a high symptom burden and a poor health-related quality of life (HRQoL). Despite efforts to offer specialised treatment, clinical care for these patients remains suboptimal and several nonmedical needs remain unaddressed. Developing a core outcome set (COS) can help to identify a minimum set of agreed-upon outcomes that should be measured and acted-upon in clinical care.
View Article and Find Full Text PDFA growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from mice at 4 times-of-day (zeitgeber times 1, 7, 13, 19).
View Article and Find Full Text PDFObjectives: To account for the heterogeneity of gestational diabetes (GDM), this study investigated tailored predictors during pregnancy and at 6-8 weeks postpartum of glucose intolerance (GI) at 1-year postpartum. We identified predictors according to data-driven clusters, analogous to the newly proposed diabetes classification, and for clinical ease also based on BMI-categories.
Methods: This is a secondary analysis of the MySweetheart trial.
With the increasing prevalence of diabetes, we are more frequently confronted to treat pregnant women with pre-existing type 2 diabetes. Thereby, we need to take several factors into account such as glycemic control before and during pregnancy, comorbidities such as overweight/obesity and hypertension, as well as existing complications and the need for changes in diabetes treatment. Pregnancy leads to increased insulin requirements, particularly from the second trimester onwards.
View Article and Find Full Text PDFBackground: Gestational Diabetes Mellitus (GDM) is frequently associated with chronic, low-grade inflammation. Whether this environment affects offspring anthropometry during early childhood remains to be elucidated. The aim of this study was to investigate the associations between maternal and fetal (cord blood-umbilical artery) inflammatory biomarkers and offspring weight and BMI up to 1 year in pregnancies with GDM.
View Article and Find Full Text PDFUnlabelled: A growing body of data suggests that skeletal muscle contractile function and glucose metabolism vary by time-of-day, with chronobiological effects on intrinsic skeletal muscle properties being proposed as the underlying mediator. However, no studies have directly investigated intrinsic contractile function or glucose metabolism in skeletal muscle over a 24 h circadian cycle. To address this, we assessed intrinsic contractile function and endurance, as well as contraction-stimulated glucose uptake, in isolated extensor digitorum longus and soleus from female mice at four times-of-day (Zeitgeber Times 1, 7, 13, 19).
View Article and Find Full Text PDFIntroduction: The aim of the study is to investigate prospective associations between breastfeeding and metabolic outcomes, inflammation, and bone density in women with prior gestational diabetes mellitus (GDM).
Research Design And Methods: We prospectively included 171 women with GDM from the MySweetheart trial. Women were followed during pregnancy (from 24 up to 32 weeks' gestational age) up to 1 year postpartum.
Mice with skeletal muscle-specific and inducible double knockout of the lysine acetyltransferases, p300 (E1A binding protein p300) and CBP (cAMP-response element-binding protein binding protein), referred to as i-mPCKO, demonstrate a dramatic loss of contractile function in skeletal muscle and ultimately die within 7 days. Given that many proteins involved in ATP generation and cross-bridge cycling are acetylated, we investigated whether these processes are dysregulated in skeletal muscle from i-mPCKO mice and, thus, whether they could underlie the rapid loss of muscle contractile function. Just 4-5 days after inducing knockout of p300 and CBP in skeletal muscle from adult i-mPCKO mice, there was ∼90% reduction in ex vivo contractile function in the extensor digitorum longus (EDL) and a ∼65% reduction in in vivo ankle dorsiflexion torque, as compared with wild type (WT; i.
View Article and Find Full Text PDFMitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks.
View Article and Find Full Text PDFSubcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism.
View Article and Find Full Text PDFResearch using zebrafish (Danio rerio) has begun to provide novel information in many fields, including the behavioral pharmacology of drug use and misuse. There have been limited studies on the effects of methamphetamine in adult zebrafish and the parameters of exposure (dose, test session length) have not been well-documented. Behavior following drug exposure is generally measured during relatively short sessions (6-10 min is common) in a novel tank environment.
View Article and Find Full Text PDFExercise-induced muscle adaptations vary based on exercise modality and intensity. We constructed a signalling network model from 87 published studies of human or rodent skeletal muscle cell responses to endurance or resistance exercise in vivo or simulated exercise in vitro. The network comprises 259 signalling interactions between 120 nodes, representing eight membrane receptors and eight canonical signalling pathways regulating 14 transcriptional regulators, 28 target genes and 12 exercise-induced phenotypes.
View Article and Find Full Text PDFUnlabelled: Mice with skeletal muscle-specific inducible double knockout of the lysine acetyltransferases, p300 (E1A binding protein p300) and CBP (cAMP-response element-binding protein binding protein), referred to as i-mPCKO, demonstrate a dramatic loss of contractile function in skeletal muscle and ultimately die within 7 days. Given that many proteins involved in ATP generation and cross-bridge cycling are acetylated, we investigated whether these processes are dysregulated in skeletal muscle from i-mPCKO mice and thus could underlie the rapid loss of muscle contractile function. Just 4-5 days after inducing knockout of p300 and CBP in skeletal muscle from adult i-mPCKO mice, there was ∼90% reduction in contractile function in the extensor digitorum longus (EDL) and a ∼65% reduction in ankle dorsiflexion torque, as compared to wildtype (WT; i.
View Article and Find Full Text PDFPre-pregnancy overweight and obesity are associated with increased risk for adverse outcomes, such as gestational diabetes mellitus (GDM). This study investigated weight trajectories, eating behaviors, and metabolic consequences in women with GDM during pregnancy and postpartum according to pre-pregnancy BMI. We prospectively included 464 women with GDM.
View Article and Find Full Text PDFA common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model.
View Article and Find Full Text PDFBackground: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise.
View Article and Find Full Text PDFHost-associated microbes influence host health and function and can be a first line of defence against infections. While research increasingly shows that terrestrial plant microbiomes contribute to bacterial, fungal, and oomycete disease resistance, no comparable experimental work has investigated marine plant microbiomes or more diverse disease agents. We test the hypothesis that the eelgrass (Zostera marina) leaf microbiome increases resistance to seagrass wasting disease.
View Article and Find Full Text PDFIntroduction: The impact of mitral regurgitation (MR) on valve-in-valve transcatheter aortic valve implantation (VIV-TAVI) in patients with failed bioprostheses remains unclear. The purpose of this study was to assess the prognostic impact of residual moderate MR following VIV-TAVI.
Methods: We retrospectively analyzed 127 patients who underwent VIV-TAVI between March 2010 and November 2021.
Unlabelled: Maternal consumption of a Western-style diet (mWD) during pregnancy alters fatty acid metabolism and reduces insulin sensitivity in fetal skeletal muscle. The long-term impact of these fetal adaptations and the pathways underlying disordered lipid metabolism are incompletely understood. Therefore, we tested whether a mWD chronically fed to lean, insulin-sensitive adult Japanese macaques throughout pregnancy and lactation would impact skeletal muscle oxidative capacity and lipid metabolism in adolescent offspring fed a postweaning (pw) Western-style diet (WD) or control diet (CD).
View Article and Find Full Text PDFPolyethlyenimine (PEI) was introduced 1995 as a cationic polymer for nucleic acid delivery. PEI and its derivatives are extensively used in basic research and as reference formulations in the field of polymer-based gene delivery. Despite its widespread use, the number of clinical applications to date is limited.
View Article and Find Full Text PDFIntroduction: Metabolomics produces vast quantities of data but determining which metabolites are the most relevant to the disease or disorder of interest can be challenging.
Objectives: This study sought to demonstrate how behavioral models of psychiatric disorders can be combined with metabolomics research to overcome this limitation.
Methods: We designed a preclinical, untargeted metabolomics procedure, that focuses on the determination of central metabolites relevant to substance use disorders that are (a) associated with changes in behavior produced by acute drug exposure and (b) impacted by repeated drug exposure.
Skeletal muscle loss and weakness are associated with bad prognosis and poorer quality of life in cancer patients. Tumor-derived factors have been implicated in muscle dysregulation by inducing cachexia and apoptosis. Here, we show that extracellular vesicles secreted by breast cancer cells impair mitochondrial homeostasis and function in skeletal muscle, leading to decreased mitochondrial content and energy production and increased oxidative stress.
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