Circulatory miRNAs as Correlates of Elevated Intra-Pancreatic Fat Deposition in a Mixed Ethnic Female Cohort: The TOFI_Asia Study.

Ectopic lipid accumulation, including intra-pancreatic fat deposition (IPFD), exacerbates type 2 diabetes risk in susceptible individuals. Dysregulated circulating microRNAs (miRNAs) have been identified as correlating with clinical measures of pancreatitis, pancreatic cancer and type 1 diabetes. The aim of the current study was therefore to examine the association between circulating abundances of candidate miRNAs, IPFD and liver fat deposition as quantified using magnetic resonance imaging (MRI) and spectroscopy (MRS).

Cold water immersion in recovery following a single bout resistance exercise suppresses mechanisms of miRNA nuclear export and maturation.

Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise.

Minimal adaptation of the molecular regulators of mitochondrial dynamics in response to unilateral limb immobilisation and retraining in middle-aged men.

Purpose: Mitochondrial dynamics are regulated by the differing molecular pathways variously governing biogenesis, fission, fusion, and mitophagy. Adaptations in mitochondrial morphology are central in driving the improvements in mitochondrial bioenergetics following exercise training. However, there is a limited understanding of mitochondrial dynamics in response to inactivity.

Skeletal muscle NOX4 is required for adaptive responses that prevent insulin resistance.

Reactive oxygen species (ROS) generated during exercise are considered integral for the health-promoting effects of exercise. However, the precise mechanisms by which exercise and ROS promote metabolic health remain unclear. Here, we demonstrate that skeletal muscle NADPH oxidase 4 (NOX4), which is induced after exercise, facilitates ROS-mediated adaptive responses that promote muscle function, maintain redox balance, and prevent the development of insulin resistance.

The Effect of Elevated Protein Intake on DNA Damage in Older People: Comparative Secondary Analysis of Two Randomized Controlled Trials.

A high protein intake at old age is important for muscle protein synthesis, however, this could also trigger protein oxidation with the potential risk for DNA damage. The aim of this study was to investigate whether an increased protein intake at recommended level or well above would affect DNA damage or change levels of reduced (GSH) and oxidised glutathione (GSSG) in community-dwelling elderly subjects. These analyses were performed in two randomized intervention studies, in Austria and in New Zealand.

α1-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet.

Neutrophils accumulate in insulin-sensitive tissues during obesity and may play a role in impairing insulin sensitivity. The major serine protease expressed by neutrophils is neutrophil elastase (NE), which is inhibited endogenously by α1-antitrypsin A (A1AT). We investigated the effect of exogenous (A1AT) treatment on diet-induced metabolic dysfunction.

Plasma mitochondrial derived peptides MOTS-c and SHLP2 positively associate with android and liver fat in people without diabetes.

Mitochondrial-derived peptides (MDPs) are encoded by the mitochondrial genome and hypothesised to form part of a retrograde signalling network that modulates adaptive responses to metabolic stress. To understand how metabolic stress regulates MDPs in humans we assessed the association between circulating MOTS-c and SHLP2 and components of metabolic syndrome (MS), as well as depot-specific fat mass in participants without overt type 2 diabetes or cardiovascular disease. One-hundred and twenty-five Chinese participants (91 male, 34 female) had anthropometry, whole body dual-energy X-ray absorptiometry scans and fasted blood samples analysed.

β-Catenin is required for optimal exercise- and contraction-stimulated skeletal muscle glucose uptake.

Key Points: Loss of β-catenin impairs in vivo and isolated muscle exercise/contraction-stimulated glucose uptake. β-Catenin is required for exercise-induced skeletal muscle actin cytoskeleton remodelling. β-Catenin phosphorylation during exercise may be intensity dependent.

Responsiveness of one-carbon metabolites to a high-protein diet in older men: Results from a 10-wk randomized controlled trial.

Objectives: Dietary strategies to promote successful aging are divergent. Higher-protein diets are recommended to preserve skeletal muscle mass and physical function. Conversely, increased B-vitamin intake, supporting one-carbon (1C) metabolism, reduces the risk of cognitive decline and cardiovascular disease.

Analysis of Human Faecal Host Proteins: Responsiveness to 10-Week Dietary Intervention Modifying Dietary Protein Intake in Elderly Males.

Faecal proteomics targeting biomarkers of immunity and inflammation have demonstrated clinical application for the identification of changes in gastrointestinal function. However, there are limited comprehensive analyses of the host faecal proteome and how it may be influenced by dietary factors. To examine this, the post-diet proteome of older males was analysed at the completion of a 10-week dietary intervention, either meeting the minimum dietary protein recommendations (RDA; = 9) or twice the recommended dietary allowance (2RDA, = 10).

Daily protein supplementation attenuates immobilization-induced blunting of postabsorptive muscle mTORC1 activation in middle-aged men.

Disuse-induced muscle atrophy is accompanied by a blunted postprandial response of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Conflicting observations exist as to whether postabsorptive mTORC1 pathway activation is also blunted by disuse and plays a role in atrophy. It is unknown whether changes in habitual protein intake alter mTORC1 regulatory proteins and how they may contribute to the development of anabolic resistance.

Ribosome biogenesis and degradation regulate translational capacity during muscle disuse and reloading.

Background: Translational capacity (i.e. ribosomal mass) is a key determinant of protein synthesis and has been associated with skeletal muscle hypertrophy.

MitoQ and CoQ10 supplementation mildly suppresses skeletal muscle mitochondrial hydrogen peroxide levels without impacting mitochondrial function in middle-aged men.

Purpose: Excess production of reactive oxygen species (ROS) from the mitochondria can promote mitochondrial dysfunction and has been implicated in the development of a range of chronic diseases. As such there is interest in whether mitochondrial-targeted antioxidant supplementation can attenuate mitochondrial-associated oxidative stress. We investigated the effect of MitoQ and CoQ10 supplementation on oxidative stress and skeletal muscle mitochondrial ROS levels and function in healthy middle-aged men.

High-intensity interval exercise increases humanin, a mitochondrial encoded peptide, in the plasma and muscle of men.

Humanin is a small regulatory peptide encoded within the 16S ribosomal RNA gene () of the mitochondrial genome that has cellular cyto- and metabolo-protective properties similar to that of aerobic exercise training. Here we investigated whether acute high-intensity interval exercise or short-term high-intensity interval training (HIIT) impacted skeletal muscle and plasma humanin levels. Vastus lateralis muscle biopsies and plasma samples were collected from young healthy untrained men ( = 10, 24.

Use of Human Induced Pluripotent Stem Cells and Kidney Organoids To Develop a Cysteamine/mTOR Inhibition Combination Therapy for Cystinosis.

Background: Mutations in -a gene encoding the cystine transporter cystinosin-cause the rare, autosomal, recessive, lysosomal-storage disease cystinosis. Research has also implicated cystinosin in modulating the mTORC1 pathway, which serves as a core regulator of cellular metabolism, proliferation, survival, and autophagy. In its severest form, cystinosis is characterized by cystine accumulation, renal proximal tubule dysfunction, and kidney failure.

Increased expression of the mitochondrial derived peptide, MOTS-c, in skeletal muscle of healthy aging men is associated with myofiber composition.

Mitochondria putatively regulate the aging process, in part, through the small regulatory peptide, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) that is encoded by the mitochondrial genome. Here we investigated the regulation of MOTS-c in the plasma and skeletal muscle of healthy aging men. Circulating MOTS-c reduced with age, but older (70-81 y) and middle-aged (45-55 y) men had ~1.

Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO).

Higher dietary protein intake is increasingly recommended for the elderly; however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk.

Whey Protein Supplementation Post Resistance Exercise in Elderly Men Induces Changes in Muscle miRNA's Compared to Resistance Exercise Alone.

Progressive muscle loss with aging results in decreased physical function, frailty, and impaired metabolic health. Deficits in anabolic signaling contribute to an impaired ability for aged skeletal muscle to adapt in response to exercise and protein feeding. One potential contributing mechanism could be exerted by dysregulation of microRNAs (miRNAs).

The Degree of Aminoacidemia after Dairy Protein Ingestion Does Not Modulate the Postexercise Anabolic Response in Young Men: A Randomized Controlled Trial.

Background: Resistance exercise and dietary protein stimulate muscle protein synthesis (MPS). The rate at which proteins are digested and absorbed into circulation alters peak plasma amino acid concentrations and may modulate postexercise MPS. A novel mineral modified milk protein concentrate (mMPC), with identical amino acid composition to standard milk protein concentrate (MPC), was formulated to induce rapid aminoacidemia.

Comprehensive Profiling of the Circulatory miRNAome Response to a High Protein Diet in Elderly Men: A Potential Role in Inflammatory Response Modulation.

Scope: MicroRNA are critical to the coordinated post-transcriptional regulation of gene expression, yet few studies have addressed the influence of habitual diet on microRNA expression. High protein diets impact cardiometabolic health and body composition in the elderly suggesting the possibility of a complex systems response. Therefore, high-throughput small RNA sequencing technology is applied in response to doubling the protein recommended dietary allowance (RDA) over 10 weeks in older men to examine alterations in circulating miRNAome.

Circulatory microRNAs are not effective biomarkers of muscle size and function in middle-aged men.

Loss of muscle size and strength with aging is a major cause of morbidity. Although muscle size and strength are measured by imaging or fiber cross-sectional staining and exercise testing, respectively, the development of circulatory biomarkers for these phenotypes would greatly simplify identification of muscle function deficits. MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene translation and, thereby, contribute to muscle phenotype.

Circulatory exosomal miRNA following intense exercise is unrelated to muscle and plasma miRNA abundances.

MicroRNAs (miRNAs) regulate gene expression via transcript degradation and translational inhibition, and they may also function as long distance signaling molecules. Circulatory miRNAs are either protein-bound or packaged within vesicles (exosomes). Ten young men (24.