Determinants of increased muscle insulin sensitivity of exercise-trained versus sedentary normal weight and overweight individuals.

The athlete's paradox states that intramyocellular triglyceride accumulation associates with insulin resistance in sedentary but not in endurance-trained humans. Underlying mechanisms and the role of muscle lipid distribution and composition on glucose metabolism remain unclear. We compared highly trained athletes (ATHL) with sedentary normal weight (LEAN) and overweight-to-obese (OVWE) male and female individuals.

Cold acclimation with shivering improves metabolic health in adults with overweight or obesity.

Cold acclimation increases insulin sensitivity, and some level of muscle contraction appears to be needed for provoking this effect. Here 15 men and (postmenopausal) women with overweight or obesity, the majority of whom had impaired glucose tolerance, were intermittently exposed to cold to induce 1 h of shivering per day over 10 days. We determined the effect of cold acclimation with shivering on overnight fasted oral glucose tolerance (primary outcome) and on skeletal muscle glucose transporter 4 translocation (secondary outcome).

Plasma triacylglycerol length and saturation level mark healthy aging groups in humans.

Complex lipids, essential components in biological processes, exhibit conserved age-related changes that alter membrane properties and cellular functions and are implicated as biomarkers and contributors to longevity and age-related diseases. While physical activity alleviates age-related comorbidities and physical impairments, comprehensive exploration of the underlying biological mechanisms, particularly at the level of complex lipids, remains limited. However, clinical studies suggest that physical activity may counteract these age-related lipidomic changes, presenting a promising avenue for intervention.

Development of a P magnetic resonance spectroscopy technique to quantify NADH and NAD at 3 T.

NADH and NAD act as electron donors and acceptors and NAD was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (P-MRS) method to quantify these metabolites in human skeletal muscle on a clinical 3 T MRI scanner. This new MR-sequence enables NADH and NAD+ quantification by suppressing α-ATP signal, normally overlapping with NADH and NAD.

Mechanical efficiency: associations with body composition and glycemic profile in healthy adults.

The aim of this study was to assess the association between net mechanical efficiency (NME) and body composition and glycemic profile, in middle-aged (38.3 ± 14.3 years) participants from the Quebec Family Study (QFS).

A conserved complex lipid signature marks human muscle aging and responds to short-term exercise.

Studies in preclinical models suggest that complex lipids, such as phospholipids, play a role in the regulation of longevity. However, identification of universally conserved complex lipid changes that occur during aging, and how these respond to interventions, is lacking. Here, to comprehensively map how complex lipids change during aging, we profiled ten tissues in young versus aged mice using a lipidomics platform.

The effect of preprandial versus postprandial physical activity on glycaemia: Meta-analysis of human intervention studies.

This meta-analysis aims to investigate the effect of preprandial physical activity (PA) versus postprandial PA on glycaemia in human intervention studies. Medline and Embase.com were searched until February 2023 for intervention studies in adults, directly comparing preprandial PA versus postprandial PA on glycaemia.

Advances and challenges in measuring hepatic glucose uptake with FDG PET: implications for diabetes research.

The liver plays a crucial role in the control of glucose homeostasis and is therefore of great interest in the investigation of the development of type 2 diabetes. Hepatic glucose uptake (HGU) can be measured through positron emission tomography (PET) imaging with the tracer [18F]-2-fluoro-2-deoxy-D-glucose (FDG). HGU is dependent on many variables (e.

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes.

Cotadutide is a dual glucagon-like peptide 1 and glucagon receptor agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes mellitus (T2DM) and chronic kidney disease. Non-alcoholic steatohepatitis is a complex disease with no approved pharmacotherapies, arising from an underlying state of systemic metabolic dysfunction in association with T2DM and obesity. Cotadutide has been shown to improve glycaemic control, body weight, lipids, liver fat, inflammation and fibrosis.

Exercise training modifies skeletal muscle clock gene expression but not 24-hour rhythmicity in substrate metabolism of men with insulin resistance.

Twenty-four hour rhythmicity in whole-body substrate metabolism, skeletal muscle clock gene expression and mitochondrial respiration is compromised upon insulin resistance. With exercise training known to ameliorate insulin resistance, our objective was to test if exercise training can reinforce diurnal variation in whole-body and skeletal muscle metabolism in men with insulin resistance. In a single-arm longitudinal design, 10 overweight and obese men with insulin resistance performed 12 weeks of high-intensity interval training recurrently in the afternoon (between 14.

The impact of prolonged fasting on 24h energy metabolism and its 24h rhythmicity in healthy, lean males: A randomized cross-over trial.

Objective: Human energy expenditure and substrate oxidation are under circadian control and food intake is a time cue for the human biological clock, leading to 24h feeding-fasting cycles in energy and substrate metabolism. In recent years, (intermittent) fasting protocols have also become popular to improve metabolic health. Here, we aimed to investigate the impact of food intake on the 24h patterns of energy metabolism as well as to provide data on the timeline of changes in energy metabolism that occur upon an extended period of fasting.

The tissue-specific metabolic effects of the PPARα agonist ciprofibrate in insulin-resistant male individuals: a double-blind, randomized, placebo-controlled crossover study.

Objective: Insulin resistance is characterized by ectopic fat accumulation leading to cardiac diastolic dysfunction and nonalcoholic fatty liver disease. The objective of this study was to determine whether treatment with the peroxisome proliferator-activated receptor-α (PPARα) agonist ciprofibrate has direct effects on cardiac and hepatic metabolism and can improve insulin sensitivity and cardiac function in insulin-resistant volunteers.

Methods: Ten insulin-resistant male volunteers received 100 mg/d of ciprofibrate and placebo for 5 weeks in a randomized double-blind crossover study.

A metabolomic signature of decelerated physiological aging in human plasma.

The degenerative processes that occur during aging increase the risk of disease and impaired health. Meanwhile, interventions that target aging to promote healthy longevity are gaining interest, both academically and in the public. While nutritional and physical interventions exist, efficacy is often difficult to determine.

PCr/ATP ratios and mitochondrial function in the heart. A comparative study in humans.

Cardiac energy status, measured as phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio with 31P-Magnetic Resonance Spectroscopy (31P-MRS) in vivo, is a prognostic factor in heart failure and is lowered in cardiometabolic disease. It has been suggested that, as oxidative phosphorylation is the major contributor to ATP synthesis, PCr/ATP ratio might be a reflection of cardiac mitochondrial function. The objective of the study was to investigate whether PCr/ATP ratios can be used as in vivo marker for cardiac mitochondrial function.

Twenty-four hour rhythmicity in mitochondrial network connectivity and mitochondrial respiration; a study in human skeletal muscle biopsies of young lean and older individuals with obesity.

Mitochondrial network dynamics may play role in metabolic homeostasis. Whether mitochondrial network dynamics are involved in adaptations to day-night fluctuations in energy supply and demand is unclear. Here we visualized and quantified the mitochondrial network morphology in human skeletal muscle of young healthy lean and older individuals with obesity over the course of 24 h METHODS: Muscle biopsies taken at 5 timepoints over a 24-hour period obtained from young healthy lean and older metabolically impaired obese males were analyzed for mitochondrial network integrity with confocal laser scanning microscopy.

Replacing Foods with a High-Glycemic Index and High in Saturated Fat by Alternatives with a Low Glycemic Index and Low Saturated Fat Reduces Hepatic Fat, Even in Isocaloric and Macronutrient Matched Conditions.

Background: Current guidelines aim to limit the dietary glycemic index (GI) and intake of saturated fatty acids (SFA). Several studies have shown favorable effects of low-GI or low-SFA diets on intrahepatic lipid content (IHL), but these studies were performed under overfeeding conditions or extreme differences in GI or SFA to maximize the contrast between diets. By combining changes in GI and SFA, we can mimic how people can improve their diet in a realistic setting.

A prolonged fast improves overnight substrate oxidation without modulating hepatic glycogen in adults with and without nonalcoholic fatty liver: A randomized crossover trial.

Objective: Increasing overnight fasting time seems a promising strategy to improve metabolic health in individuals with nonalcoholic fatty liver (NAFL). Mechanisms underlying the beneficial effects of fasting may be related to larger fluctuations in hepatic glycogen and higher fat oxidation. This study investigated whether prolonging an overnight fast depletes hepatic glycogen stores and improves substrate metabolism in individuals with NAFL and healthy lean individuals.

Effect of β2-agonist treatment on insulin-stimulated peripheral glucose disposal in healthy men in a randomised placebo-controlled trial.

β-agonist treatment improves skeletal muscle glucose uptake and whole-body glucose homeostasis in rodents, likely via mTORC2-mediated signalling. However, human data on this topic is virtually absent. We here investigate the effects of two-weeks treatment with the β-agonist clenbuterol (40 µg/day) on glucose control as well as energy- and substrate metabolism in healthy young men (age: 18-30 years, BMI: 20-25 kg/m) in a randomised, placebo-controlled, double-blinded, cross-over study (ClinicalTrials.

Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial.

Aims/hypothesis: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment in type 2 diabetes mellitus patients results in glucosuria, causing an energy loss, and triggers beneficial metabolic adaptations. It is so far unknown if SGLT2i exerts beneficial metabolic effects in prediabetic insulin resistant individuals, yet this is of interest since SGLT2is also reduce the risk for progression of heart failure and chronic kidney disease in patients without diabetes.

Methods: Fourteen prediabetic insulin resistant individuals (BMI: 30.