Henriette Pilegaard's research while affiliated with IT University of Copenhagen and other places

Publications (227)

Article
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Objective: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans, in association with exercise remains to be c...
Article
Extrachromosomal circular DNA (eccDNA) of chromosomal origin is common in eukaryotic cells. Amplification of oncogenes on large eccDNA (ecDNA) can drive biological processes such as tumorigenesis, and identification of eccDNA by sequencing after removal of chromosomal DNA is therefore important for understanding their impact on the expressed phenot...
Article
The circadian rhythm has profound effect on the body, exerting effects on diverse events like sleep-wake patterns, eating behavior and hepatic detoxification. The cytochrome p450 s (Cyps) is the main group of enzymes responsible for detoxification. However, the underlying mechanisms behind circadian regulation of the Cyps are currently not fully cl...
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Growing old is patently among the most prominent risk factors for lifestyle related diseases and deterioration in physical performance. Aging in particular affects mitochondrial homeostasis and maintaining a well-functioning mitochondrial pool is imperative in order to avoid age-associated metabolic decline. White adipose tissue (WAT) is a key orga...
Article
Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant...
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The influence of glucose and palmitic acid (PA) on mitochondrial respiration and emission of hydrogen peroxide (H2 O2 ) was determined in skeletal muscle-derived microvascular endothelial cells. Measurements were assessed in intact and permeabilized (cells treated with 0.025% saponin) low passage endothelial cells with acute-or prolonged (3 days) i...
Chapter
Exercise has the ability to induce a rapid shift in metabolic demands leading to transient perturbations in whole-body homeostasis. This challenge triggers a multitude of both acute metabolic adjustments and adaptive molecular integrative responses in skeletal muscle to re-establish homeostasis. Initiating stimuli involved in inducing these respons...
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Aims/hypothesis: Growth hormone (GH) causes insulin resistance that is linked to lipolysis, but the underlying mechanisms are unclear. We investigated if GH-induced insulin resistance in skeletal muscle involves accumulation of diacylglycerol (DAG) and ceramide as well as impaired insulin signalling, or substrate competition between fatty acids an...
Article
Gut hormones affect cardiac function and contractility. In this study, we examined whether insulin affects the cardiac atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression and release of proANP-derived peptides in pigs. Anaesthetized pigs were included in an experimental study comparing the effect of hyperinsulinemi...
Article
The majority of human energy metabolism occurs in skeletal muscle mitochondria emphasizing the importance of understanding the regulation of myocellular mitochondrial function. The transcriptional co-activator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) has been characterized as a major factor in the transcriptiona...
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Objective Current evidence for AMPK-mediated regulation of skeletal muscle metabolism during exercise is mainly based on transgenic mouse models with chronic (lifelong) disruption of AMPK function. Findings based on such models are potentially biased by secondary effects related to chronic lack of AMPK function. In an attempt to study the direct ef...
Article
The aim of the study was to investigate the impact of autophagy inhibition on skeletal muscle mitochondrial function and glucose homeostasis in young and aged mice. The transcriptional co‐activator PGC‐1α regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle...
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White adipose tissue is a major energy reserve for the body and is essential for providing fatty acids for other tissues when needed. Skeletal muscle interleukin-6 (IL-6) has been shown to be secreted from the working muscle and has been suggested to signal to adipose tissue and enhance lipolysis. The aim of the present study was to investigate the...
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Abstract Fasting in human subjects shifts skeletal muscle metabolism toward lipid utilization and accumulation, including intramyocellular lipid (IMCL) deposition. Growth hormone (GH) secretion amplifies during fasting and promotes lipolysis and lipid oxidation, but it is unknown to which degree lipid deposition and metabolism in skeletal muscle du...
Article
Fasting has been shown to regulate the expression of the cytochrome p450 (CYP) enzyme system in the liver. However, the exact mechanism behind the fasting-induced regulation of the CYP's remains unknown. In the present study we tested the hypothesis that the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), which is a key-re...
Article
Impaired mitochondrial function has been implicated in the pathogenesis of age-associated metabolic diseases through regulation of cellular redox balance. Exercise training is known to promote mitochondrial biogenesis in part through induction of the transcriptional co-activator PGC-1α. Recently, mitochondrial ADP sensitivity has been linked to ROS...
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Lifelong regular physical activity is associated with reduced risk of type 2 diabetes (T2D), maintenance of muscle mass and increased metabolic capacity. However, little is known about epigenetic mechanisms that might contribute to these beneficial effects in aged individuals. We investigated the effect of lifelong physical activity on global DNA m...
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This study examined adaptations in muscle oxidative capacity and exercise performance induced by two work- and duration-matched exercise protocols eliciting different muscle metabolic perturbations in trained individuals. Thirteen male subjects ( V ˙ O2 -max 53.5 ± 7.0 mL·kg-1 ·min-1 ) (means ± SD) performed 8 weeks (three sessions/week) of trai...
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The liver and adipose tissue are important tissues in whole-body metabolic regulation during fasting. Interleukin 6 (IL-6) is a cytokine shown to be secreted from contracting muscle in humans and suggested to signal to the liver and adipose tissue. Furthermore, skeletal muscle IL-6 has been proposed to play a role during fasting. Therefore the aim...
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The aim of the present study was to examine the influence of training state on fasting-induced skeletal muscle pyruvate dehydrogenase (PDH) regulation, including PDH phosphorylation. Trained and untrained subjects, matched for skeletal muscle CS activity and OXPHOS protein, fasted for 36 h after receiving a standardized meal. Respiratory exchange r...
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The aim of this study was to examine the effect of exercise training and dietary supplementation of resveratrol on the composition of gut microbiota and to test the hypothesis that exercise training and resveratrol can prevent high‐fat diet (HFD)‐induced changes in the gut microbiota. Mice fed a HFD supplemented with resveratrol (4 g/kg food) were...
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The aim of the present study was to test the hypothesis that PGC-1α is involved in the regulation of hepatic UPR and autophagy in response to both exercise and fasting in mice. Liver-specific PGC-1α knockout (LKO) mice and their floxed littermates (lox/lox) were used in two experimental parts. Liver and plasma were obtained from (1) fed and 18 h fa...
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Diet-induced obesity is associated with hepatic steatosis, which has been linked with activation of the unfolded protein response (UPR). PGC-1α is a transcriptional coactivator involved in exercise training-induced adaptations in muscle and liver. Therefore, the aim of this study was to test the hypothesis that PGC-1α is required for exercise train...
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Hepatic autophagy has been shown to be regulated by acute exercise and exercise training. Moreover, high‐fat diet‐induced steatosis has been reported to be associated with impaired hepatic autophagy. In addition, autophagy has been shown to be regulated by acute exercise and exercise training in a PGC‐1α dependent manner in skeletal muscle. The aim...
Article
Exercise training has been reported to prevent the age-induced decline in muscle mass and fragmentation of mitochondria, as well as to affect autophagy and mitophagy. The interaction between these pathways during aging as well as the similarity between changes in markers in human and mouse skeletal muscle is however not fully understood. Therefore...
Article
Key points: Animal models have shown that beta2 -adrenoceptor stimulation increases protein synthesis and attenuates breakdown processes in skeletal muscle. Thus, the beta2 -adrenoceptor is a potential target in the treatment of disuse-, disease- and age-related muscle atrophy. In the present study, we show that a few days of oral treatment with t...
Article
Aim To provide a detailed time course of hepatic autophagy and all UPR branches in response to an acute bout of exercise and 24h of fasting, and test the hypothesis that muscle‐specific PGC‐1α overexpression dampens the UPR and autophagy responses to these metabolic challenges. Methods Muscle‐specific PGC‐1α overexpression (TG) and wild‐type (WT)...
Article
Key points: Low-volume high-intensity exercise training promotes muscle mitochondrial adaptations that resemble those associated with high-volume moderate-intensity exercise training. These training-induced mitochondrial adaptations stem from the cumulative effects of transient transcriptional responses to each acute exercise bout. However, whethe...
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Moderately trained male subjects (mean age 25 years; range 19-33 years) completed an 8-week exercise training intervention consisting of continuous moderate cycling at 157 ± 20 W for 60 min (MOD; n = 6) or continuous moderate cycling (157 ± 20 W) interspersed by 30-sec sprints (473 ± 79 W) every 10 min (SPRINT; n = 6) 3 days per week. Sprints were...
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The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16 he...
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An acute bout of exercise imposes a major challenge on whole-body metabolism and metabolic adjustments are needed in multiple tissues during recovery to reestablish metabolic homeostasis. It is currently unresolved how this regulation is orchestrated between tissues. This study was undertaken to clarify the role of skeletal muscle derived interleuk...
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Pyruvate dehydrogenase (PDH) is the gateway enzyme for carbohydrate-derived pyruvate feeding into the TCA cycle. PDH may play a central role in regulating substrate shifts during exercise, but the influence of training state on PDH regulation during exercise is not fully elucidated. The purpose of this study was to investigate the impact of trainin...
Article
Recruitment of fatty acids from adipose tissue is increased during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore the aim of the present study was to investigate 1) fasting-induced regulation of lipolysis and gly...
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The aim of the present study was to examine the role of PGC-1α in intensity dependent exercise and exercise training-induced metabolic adaptations in mouse skeletal muscle. Whole body PGC-1α knockout (KO) and littermate wildtype (WT) mice performed a single treadmill running bout at either low intensity (LI) for 40 min or moderate intensity (MI) fo...
Article
mRNA expression of the cytochrome P450 (CYP) enzyme family is regulated by numerous factors. Fasting has been shown to induce increased hepatic CYP mRNA in both humans and animals. However, the coordinated regulation of CYP, CYP-regulating transcription factors, and transcriptional co-factors in the liver linking energy metabolism to detoxification...
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PGC-1α has been suggested to regulate exercise training-induced metabolic adaptations and autophagy in skeletal muscle. The factors regulating PGC-1α are however not fully resolved. The aim was to investigate the impact of β-adrenergic signaling in PGC-1α mediated metabolic adaptations in skeletal muscle with exercise training. Muscle was obtained...
Article
To understand the mechanisms in lipid-induced insulin resistance, a more physiologic approach is to enhance FA availability through the diet. Nine healthy men ingested two hypercaloric diets (+75 E%) for three days, enriched in unsaturated FA (78 E% fat; UNSAT) or carbohydrates (80 E% carbohydrate; CHO) as well as a eucaloric control diet (CON). Co...
Article
Aging is associated with changes in several metabolic pathways affecting liver function including the adaptive unfolded protein response (UPR). On the other hand, exercise training has been shown to exert beneficial effects on metabolism including the liver and exercise training has been reported to affect hepatic UPR. PGC-1α is a transcriptional c...
Article
Aging is associated with impaired mitochondrial function, whereas exercise training enhances mitochondrial content and function in part through activation of PGC-1α. Mitochondria form dynamic networks regulated by fission and fusion with profound effects on mitochondrial functions, yet the effects of aging and exercise training on mitochondrial net...
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The purpose of the present study was to examine whether lack of skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) affects the switch in substrate utilization from a fed to fasted state and the fasting-induced pyruvate dehydrogenase (PDH) regulation in skeletal muscle. Skeletal muscle-specific PGC-1α knock...
Article
Exercise has long been recognized as a powerful physiological stimulus for a wide variety of metabolic adaptations with implications for health and performance. The metabolic effects of exercise occur during and after each exercise bout and manifest as cumulative adaptive responses to successive exercise bouts. Studies on the beneficial effects of...
Article
Aim: the liver is essential in maintaining and regulating glucose homeostasis during exercise. Interleukin 6(IL-6) has been shown to be secreted from skeletal muscle during exercise and has been suggested to signal to the liver. Therefore, the aim was to investigate the role of skeletal muscle IL-6 on hepatic glucose regulation and substrate choic...
Article
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Fasting prompts a metabolic shift in substrate utilization from carbohydrate to predominant fat oxidation in skeletal muscle and pyruvate dehydrogenase (PDH) is seen as a controlling link between the competitive oxidation of carbohydrate and fat during metabolic challenges like fasting. Interleukin (IL)-6 has been proposed to be released from muscl...
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The aim of this study was to investigate the mRNA response related to mitochondrial biogenesis, metabolism, angiogenesis, and myogenesis in trained human skeletal muscle to speed endurance exercise (S), endurance exercise (E), and speed endurance followed by endurance exercise (S + E). Seventeen trained male subjects (maximum oxygen uptake (VO2-max...
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This study tested the hypothesis that elevated plasma adrenaline or metabolic stress enhances exercise-induced PGC-1α mRNA and intracellular signaling in human muscle. Trained (VO2-max: 53.8 ± 1.8 mL min(-1) kg(-1)) male subjects completed four different exercise protocols (work load of the legs was matched): C - cycling at 171 ± 6 W for 60 min (co...
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Pyruvate dehydrogenase (PDH) plays a key role in the regulation of skeletal muscle substrate utilization. IL-6 is produced in skeletal muscle during exercise in a duration dependent manner and has been reported to increase whole body fatty acid oxidation, muscle glucose uptake and decrease PDHa activity in skeletal muscle of fed mice. The aim of th...
Data
Representative PCR gel of products generated with primers surrounding exon 2 of the IL-6 gene in quadriceps muscle from floxed and IL-6 skeletal muscle-specific knockout mice. A reduction in band size from 1,000 bp to 260 bp in is equal to the loss of exon 2 of the IL-6 gene. WT Ctrl: Wild-type control, Flox Ctrl: Floxed control, MKO Control: Skele...
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Interleukin (IL)-6 is released from skeletal muscle (SkM) during exercise and has been shown to affect hepatic metabolism. It is, however, unknown whether SkM IL-6 is involved in the regulation of exercise training-induced counteraction of changes in carbohydrate and lipid metabolism in the liver in response to high-fat diet (HFD) feeding. Male SkM...