Recent advances in exercise immunometabolism: Immune cell bioenergetics, muscle-immune cell interactions, and potential dietary adjuvants.

Purpose Of Review: Exercise profoundly alters immunological processes to improve overall health and immunity. The link between immune cell metabolism and function has prompted study of immune cell bioenergetics following acute exercise and the role of muscle-resident immune cells in training adaptations. This review highlights recent work in the area and discusses potential dietary approaches for boosting exercise-induced immunometabolic benefits.

Technology-Enabled Exercise "Snacks" Are Feasible to Perform in a Real-World Setting: A Randomized Controlled Trial.

This randomized controlled trial investigated the feasibility and efficacy of a 12-week remotely delivered exercise snacks intervention in the real world. Inactive adults (n = 77; 56 females, 21 males; mean age ± SD: 54 ± 6 years, mean VO ± SD: 24.5 ± 4.

Altered immunometabolic response to fasting in humans living with obesity.

Fasting and ketosis are gaining interest for treating obesity-related immunometabolic dysfunction. We aimed to (1) characterize systemic and T cell immunometabolic responses to a 48-h fast in humans and (2) determine if responses differed between individuals with (O-BMI) and without (L-BMI) obesity (n = 16 per group). Despite similar increases in systemic fat oxidation, increases in blood β-hydroxybutyrate (BHB), BHB-amino acid conjugates, and lysine β-hydroxybutyrylation were blunted in obesity.

Mitochondrial and cardiovascular responses to aerobic exercise training in supine and upright positions in healthy young adults: a randomized parallel arm trial.

Objectives: Aerobic exercise training can increase skeletal muscle mitochondrial content. Supine exercise training with legs above the heart potentially augments these increases. However, the impact of supine exercise training on mitochondrial biogenesis and cardiovascular adaptations remains unclear.

Do Exercise Pattern and Intensity Influence Affective and Enjoyment Responses in Active Adults? A Secondary Analysis.

The purpose of the present study was to compare the ratings of perceived exertion (RPE), affective (Feeling Scale), and remembered enjoyment (Physical Activity Enjoyment Scale) responses following different exercise intensities/patterns and to investigate possible associations with physiological parameters in active adults. In a randomized crossover trial, 16 active adults (29.9 ± 3.

Changes in plasma cytokines following a 60-h fast are not influenced by the addition of exercise despite elevated ketones in healthy young adults.

Immunometabolic processes maintain physiological homeostasis and are implicated in various chronic diseases. Fasting and exercise independently alter metabolic and immunological processes; their combination could provide insights into immunometabolic interactions. Using a randomized crossover design, 15 healthy adults (six females, nine males, 26.

Interleukin-10 resistance in type 2 diabetes is associated with defective STAT3 signaling in human blood leukocytes.

Chronic inflammation is strongly implicated in the pathophysiology of type 2 diabetes (T2D), highlighting the need to better understand inflammatory processes in people living with T2D. Hyperglycemia blunts the anti-inflammatory actions of interleukin-10 (IL-10)-the most potent anti-inflammatory cytokine-but the mechanistic basis remains unclear. To test the hypothesis that signaling defects underpin this hyporesponsiveness to IL-10 action, fasted blood samples were obtained from individuals living with T2D ( = 17, age: 64 ± 9 yr, HbA1c: 7.

Extracellular ATP regulates phagocytic activity, mitochondrial respiration, and cytokine secretion of human astrocytic cells.

The two main glial cell types of the central nervous system (CNS), astrocytes and microglia, are responsible for neuroimmune homeostasis. Recent evidence indicates astrocytes can participate in removal of pathological structures by becoming phagocytic under conditions of neurodegenerative disease when microglia, the professional phagocytes, are impaired. We hypothesized that adenosine triphosphate (ATP), which acts as damage-associated molecular pattern (DAMP), when released at high concentrations into extracellular space, upregulates phagocytic activity of human astrocytes.

Cross-sectional analysis of blood leukocyte responsiveness to interleukin-10 and interleukin-6 across age and physical activity level.

Objectives: To determine how the anti-inflammatory actions of interleukin-10 (IL-10) and IL-6 differ across age and physical activity levels.

Methods: Using a cross-sectional design, fasted blood samples were obtained from younger physically inactive (YI: n=10, age: 22.7 ± 3.

Impact of exercise and fasting on mitochondrial regulators in human muscle.

Objectives: To investigate the impact of acute energetic stress (acute HIIE and fasting) on , , , , and in human skeletal muscle.

Methods: The current study performed secondary analyses using muscle biopsy samples from two previously published studies: study 1) leg muscle biopsies from nine men and eight women were obtained pre and 3 h following acute high-intensity interval cycling exercise (HIIE); study 2) leg muscle biopsies were obtained from nine men pre-, during, and post-an 8 h fast with or without 2 h of arm ergometer exercise. RT-PCR was performed on samples from each study to determine the mRNA expression of , , , , and .

A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites.

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids.

Elevated Plasma IL-6 Coincides with Activation of STAT3 in PBMC After Acute Resistance Exercise.

Introduction: Changes in plasma concentrations of anti-inflammatory cytokines, such as interleukin-6 (IL-6) and IL-10, after acute resistance exercise (RE) have been widely explored. Whether observed changes in plasma cytokine concentration correspond to the activation of anti-inflammatory signaling pathways in immune cells after acute RE is unknown. This study aimed to determine if changes in plasma cytokines after acute RE resulted in the activation of anti-inflammatory signaling pathways in peripheral blood mononuclear cells (PBMC).

A secondary β-hydroxybutyrate metabolic pathway linked to energy balance.

β-hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve interconversion of BHB and primary energy intermediates. Here we show that CNDP2 controls a previously undescribed secondary BHB metabolic pathway via enzymatic conjugation of BHB and free amino acids.

A secondary analysis of indices of hepatic and beta cell function following 12 weeks of carbohydrate and energy restriction vs. free-living control in adults with type 2 diabetes.

Background: Substantial weight loss in people living with type 2 diabetes (T2D) can reduce the need for glucose-lowering medications while concurrently lowering glycemia below the diagnostic threshold for the disease. Furthermore, weight-loss interventions have also been demonstrated to improve aspects of underlying T2D pathophysiology related to ectopic fat in the liver and pancreatic beta-cell function. As such, the purpose of this secondary analysis was to explore the extent to which a low-carbohydrate and energy-restricted (LCER) diet intervention improves markers of beta-cell stress/function, liver fat accumulation, and metabolic related liver function in people with type 2 diabetes.

Direct assessment of leukocyte signalling and cytokine secretion reveals exercise intensity-dependent reductions in anti-inflammatory cytokine action.

Circulating interleukin (IL)-6 and IL-10 concentrations are widely used to evaluate the anti-inflammatory effects of exercise but do not capture cytokine action at the cellular level. Whether and how acute exercise impacts anti-inflammatory cytokine action in humans is unknown. To determine how exercise intensity and pattern impact IL-6 and IL-10 action in blood leukocytes, 16 active adults (eight males/eight females; age: 30 ± 3 years; body mass index: 22.

Differential changes in appetite hormones post-prandially based on menstrual cycle phase and oral contraceptive use: A preliminary study.

This was a preliminary study that examined whether appetite regulation is altered during the menstrual cycle or with oral contraceptives. Ten naturally cycling females (NON-USERS) and nine tri-phasic oral contraceptive using females (USERS) completed experimental sessions during each menstrual phase (follicular phase: FP; ovulatory phase: OP; luteal phase: LP). Appetite perceptions and blood samples were obtained fasted, 30, 60, and 90 min post-prandial to measure acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and total peptide tyrosine tyrosine (PYY).

Effect of the ketone beta-hydroxybutyrate on markers of inflammation and immune function in adults with type 2 diabetes.

Pre-clinical and cell culture evidence supports the role of the ketone beta-hydroxybutyrate (BHB) as an immunomodulatory molecule that may inhibit inflammatory signalling involved in several chronic diseases such as type 2 diabetes (T2D), but studies in humans are lacking. Therefore, we investigated the anti-inflammatory effect of BHB in humans across three clinical trials. To investigate if BHB suppressed pro-inflammatory cytokine secretion, we treated LPS-stimulated leukocytes from overnight-fasted adults at risk for T2D with BHB (Study 1).

Intense exercise at high altitude causes platelet loss across the brain in humans.

Platelets are known primarily for their role in blood clotting; however, it is becoming clear that they play diverse roles beyond that of haemostasis. Exercise has been shown to activate platelets and stimulate neurogenesis, neuroplasticity and improve cognitive function, highlighting a potentially powerful link between platelet function and brain health. Despite this clear link between platelets and the brain, very little is known about the behaviour of platelets through the cerebral circulation in humans.

Creating your own line: reflections from early career scientists.

The changing landscape of academia can be difficult to navigate for anyone at any point throughout their career. One thing is certainly clear: effective mentorship is key to ensuring success, fueling scientific curiosity, and creating a sense of community. This article is a collection of personal reflections and stories, offering advice directed to aspiring and junior graduate trainees; it is written by Ph.

Skeletal muscle mechanisms contributing to improved glycemic control following intense interval exercise and training.

High-intensity and sprint interval training (HIIT and SIT, respectively) enhance insulin sensitivity and glycemic control in both healthy adults and those with cardiometabolic diseases. The beneficial effects of intense interval training on glycemic control include both improvements seen in the hours to days following a single session of HIIT/SIT and those which accrue with chronic training. Skeletal muscle is the largest site of insulin-stimulated glucose uptake and plays an integral role in the beneficial effects of exercise on glycemic control.

Exogenous ketone supplementation: an emerging tool for physiologists with potential as a metabolic therapy.

New Findings: What is the topic of this review? The integrative physiological response to exogenous ketone supplementation. What advances does it highlight? The physiological effects and therapeutic potential of exogenous ketones on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. Also highlighted are current challenges and future directions of the field.

Oral ketone monoester supplementation does not accelerate recovery of muscle force or modulate circulating cytokine concentrations after muscle-damaging eccentric exercise in healthy males and females.

New Findings: What is the central question of this study? Does acute ketone monoester supplementation enhance the recovery of muscle force and modulate circulating cytokine concentrations after muscle-damaging eccentric exercise? What is the main finding and its importance? Ketone monoester supplementation increased plasma β-hydroxybutyrate concentrations but did not attenuate the reduction in muscle force or the increase in plasma inflammatory cytokine concentrations that occurred after eccentric exercise. Notably we report novel data demonstrating a reduction in plasma TRAIL concentrations after eccentric exercise, highlighting TRAIL signalling as a possibly novel regulator of muscle recovery.

Abstract: Muscle-damaging eccentric exercise is associated with inflammation and impaired muscle force.

Impacts of altered exercise volume, intensity, and duration on the activation of AMPK and CaMKII and increases in PGC-1α mRNA.

The purpose of this review is to explore and discuss the impacts of augmented training volume, intensity, and duration on the phosphorylation/activation of key signaling protein - AMPK, CaMKII and PGC-1α - involved in the initiation of mitochondrial biogenesis. Specifically, we explore the impacts of augmented exercise protocols on AMP/ADP and Ca signaling and changes in post exercise PGC - 1α gene expression. Although AMP/ADP concentrations appear to increase with increasing intensity and during extended durations of higher intensity exercise AMPK activation results are varied with some results supporting and intensity/duration effect and others not.