
Carlos Henríquez-Olguín- PhD in Molecular Physiology
- Assistant Professor at University of Copenhagen
Carlos Henríquez-Olguín
- PhD in Molecular Physiology
- Assistant Professor at University of Copenhagen
Deciphering Intracellular Signaling in Skeletal Muscle
About
92
Publications
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Introduction
Dedicated and purpose-driven scientist studying the role of skeletal muscle in metabolism at both single-cell and whole-body levels. Our research focuses on connecting intracellular redox signaling and skeletal muscle metabolism in the context of exercise and metabolic diseases.
Current institution
Additional affiliations
Education
March 2015 - August 2018
March 2014 - December 2018
March 2010 - July 2013
Publications
Publications (92)
Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers, mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo, but whether myocellular ROS production is stimulated...
Decline in mitochondrial function is linked to decreased muscle mass and strength in conditions like sarcopenia and type 2 diabetes. Despite therapeutic opportunities, there is limited and equivocal data regarding molecular cues controlling muscle mitochondrial plasticity. Here we uncovered that the mitochondrial mRNA-stabilizing protein SLIRP, in...
Preclinical models suggest mitochondria-derived oxidative stress as an underlying cause of insulin resistance. However, it remains unknown whether this pathophysiological mechanism is conserved in humans. Here, we used an invasive in vivo mechanistic approach to interrogate muscle insulin action while selectively manipulating the mitochondrial redo...
Purpose Blocking the Activin receptor type IIA and B (ActRIIA/IIB) has clinical potential to increase muscle mass and improve glycemic control in obesity, cancer, and aging. However, the impact of blocking ActRIIA/IIB on strength, metabolic regulation and insulin action remains unclear. Methods Here, we investigated the effect of short- (10 mg/kg o...
The kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between in...
Context
Housing temperature is a critical regulator of mouse metabolism and thermoneutral housing can improve model translation to humans. However, the impact of housing temperature on the ability of wheel running exercise training to rescue the detrimental effect of diet-induced obese mice is currently not fully understood.
Objective
To investiga...
Aim: The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM).
Methods: Eight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex...
Reactive oxygen species (ROS) are well‐established signaling molecules implicated in a wide range of cellular processes, including both oxidative stress and intracellular redox signaling. In the context of insulin action within its target tissues, ROS have been reported to exert both positive and negative regulatory effects. However, the precise mo...
Decline in mitochondrial function associates with decreased muscle mass and strength in multiple conditions, including sarcopenia and type 2 diabetes. Optimal treatment could include improving mitochondrial function, however, there are limited and equivocal data regarding the molecular cues controlling muscle mitochondrial plasticity. Here we uncov...
and graphical abstract
The decline in mitochondrial function is associated with decreased muscle mass and strength in multiple conditions, including sarcopenia, type 2 diabetes, and cancer. Treatment of these diseases could include improving mitochondrial function, however, there are limited and equivocal data regarding the molecular cues that cont...
Exercise training elicits tremendous health benefits; however, the molecular underpinnings are poorly understood. As one of the most regulated groups of proteins following acute exercise in human muscle, Rho GTPases are unexplored candidates for mediating the beneficial effects of exercise. The Rho GTPase Rac1 was activated during multiple exercise...
The production of reactive oxygen species (ROS) by NADPH oxidase (NOX) 2 has been linked to both insulin resistance and exercise training adaptations in skeletal muscle. This study explores the previously unexamined role of NOX2 in the interplay between diet-induced insulin resistance and exercise training (ET). Using a mouse model that harbors a p...
The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin s...
Background:
Metabolic dysfunction and cachexia are associated with poor cancer prognosis. With no pharmacological treatments, it is crucial to define the molecular mechanisms causing cancer-induced metabolic dysfunction and cachexia. Adenosine monophosphate-activated protein kinase (AMPK) connects metabolic and muscle mass regulation. As AMPK coul...
Skeletal muscle atrophy has been linked to physical inactivity and aging, conditions characterized by the presence of oxidative stress. While several reactive oxygen species (ROS) sources and changes in the antioxidant network have been described, the relative contribution of mitochondrial and cytosolic compartments is unknown. This project optimiz...
Introduction: Mice are extensively used to investigate the molecular foundations of obesity and the beneficial effect of exercise training (ET). Mice are most often housed at ambient temperature, ~22°C, which is below their thermoneutral environment (~30°C). Mild cold stress at ambient temperature accelerates mouse metabolic rate and may confound t...
Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based GLUT4 trafficking in human and mouse muscle fibers and L6 rat muscle cells. We found GLUT4 loc...
Pre-clinical models indicate a causative nexus between mitochondrial oxidative stress and insulin resistance. However, the pathophysiological significance of this mechanism in humans remains unproven. Herein, we employed an invasive in vivo mechanistic approach in humans to manipulate mitochondrial redox state while assessing insulin action. To thi...
Microtubules serve as tracks for long-range intracellular trafficking of glucose transporter 4 (GLUT4), but the role of this process in skeletal muscle and insulin resistance is unclear. Here, we used fixed and live-cell imaging to study microtubule-based GLUT4 trafficking in human and mouse muscle fibers and L6 rat muscle cells. We found GLUT4 loc...
Muscle glucose uptake during exercise is regulated by a coordinated increase in glucose delivery (via increased blood flow and glucose moving out of the capillaries into the interstitial space), by facilitated glucose transport into the myocytes and by intramyocellular metabolism. The facilitative glucose transporter GLUT4 is translocated to the sa...
Background
Metabolic dysfunction and cancer cachexia are associated with poor cancer prognosis, yet the molecular mechanisms causing cancer-induced metabolic dysfunction and cachexia remain to be defined. A key link between metabolic- and muscle mass-regulation is adenosine monophosphate-activated protein kinase (AMPK). As AMPK could be a potential...
Significance
The function of tissues is controlled by complex biological processes, in which transcriptional mechanisms play a fundamental role. The transcriptional coactivator PGC-1α is a prototypical regulator of adaptive responses evoked by environmental and internal cues (e.g. exercise-adaptation in skeletal muscle). Here, we found that PGC-1α-...
High-intensity muscle contractions (HiMC) are known to increase c-Myc expression which is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, while c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, thi...
Key points
Tamoxifen‐inducible skeletal muscle‐specific AXIN1 knockout (AXIN1 imKO) in mouse does not affect whole‐body energy substrate metabolism.
AXIN1 imKO does not affect AICAR or insulin‐stimulated glucose uptake in adult skeletal muscle.
AXIN1 imKO does not affect adult skeletal muscle AMPK or mTORC1 signalling during AICAR/insulin/amino aci...
Background: High-intensity muscle contractions (HiMC) are known to increase c-Myc expression which is known to stimulate ribosome biogenesis and protein synthesis in tumor cells. However, whether the increase in c-Myc stimulates ribosome biogenesis and protein synthesis in skeletal muscles remains unknown.
Methods: We investigated the effect of ade...
Women with polycystic ovary syndrome (PCOS) have been shown to be less insulin sensitive compared with control women, independent of BMI. Training is associated with molecular adaptations in skeletal muscle improving glucose uptake and metabolism in both healthy and type 2 diabetic individuals. In the present study, lean, hyperandrogenic women with...
Key points
AMP‐activated protein kinase (AMPK)‐dependent Raptor Ser792 phosphorylation does not influence mechanistic target of rapamycin complex 1 (mTORC1)‐S6K1 activation by intense muscle contraction.
α2‐AMPK activity‐deficient mice have lower contraction‐stimulated protein synthesis.
Increasing glycogen activates mTORC1‐S6K1.
Normalizing muscle...
Objective
Exercise is a cornerstone in the management of skeletal muscle insulin-resistance. A well-established benefit of a single bout of exercise is increased insulin sensitivity for hours post-exercise in the previously exercised musculature. Although rodent studies suggest that the insulin-sensitization phenomenon involves enhanced insulin-sti...
The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on anal...
Exercise training is a powerful means to combat metabolic diseases. Mice are extensively used to investigate the benefits of exercise, but mild cold stress induced by ambient housing temperatures may confound translation to humans. Thermoneutral housing is a strategy to make mice more metabolically similar to humans but its effects on exercise adap...
Exercise imposes cellular stress on contracting skeletal muscle fibers, forcing them to complete molecular adaptations to maintain homeostasis. There is mounting evidence that redox signaling by reactive oxygen species (ROS) is vital for skeletal muscle exercise adaptations across many different exercise modalities. The study of redox signaling is...
Background:
Redirecting glucose from skeletal muscle and adipose tissue, likely benefits the tumor's energy demand to support tumor growth, as cancer patients with type 2 diabetes have 30% increased mortality rates. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying cancer-induced metabolic per...
Significance:
Skeletal muscle is a crucial tissue to whole-body locomotion and metabolic health. Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. A complex interplay between ROS-producing enzymes and antioxidant networks exists in different su...
Cancer is often associated with poor glycemic control. However, the underlying molecular mechanisms are unknown. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying impaired glycemic regulation in cancer.
Basal and insulin-stimulated glucose uptake in skeletal muscle and white adipose tissue (WAT...
Background:
Skeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor β (TGF-β) superfamily, including activin A, which causes atrophy. TGF-β superfamily ligands also negatively regulate insulin-sensitive proteins, but whether this pathway contributes to insulin action r...
Background: Immobilization of skeletal muscle in a stretched position is associated with marked protection against disuse atrophy. Some intramyocellular changes in known proteins and post-translational modifications were previously linked to this phenomenon but there are likely many presently unknown proteins and post-translational modifications th...
Exercise training is a powerful means to combat metabolic pathologies. Mice are extensively used to describe the benefits of exercise, but mild cold stress induced by housing temperatures may confound translation to humans. Thermoneutral housing is a strategy to make mice more metabolically similar to humans but its effects on exercise adaptations...
A periodized (14 days on/14 days off) 5% low protein-high carbohydrate (pLPHC) diet protects against weight gain, improves glucose tolerance in mice and interacts with concurrent voluntary activity wheel training on several parameters including weight maintenance and liver FGF21 secretion. The gut microbiome (GM) responds to both diet and exercise...
Objective
Reactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate if increased NADPH oxidase (NOX)2-dependent activity during exercise is required for long-term high-intensity interval training (HIIT) in skeletal muscle u...
Objective: Reactive oxygen species (ROS) have been proposed as signaling molecules mediating exercise training adaptation, but the ROS source has remained unclear. This study aimed to investigate the requirement for NADPH oxidase (NOX)2-dependent redox changes induced by acute and long-term high-intensity interval training (HIIT) in skeletal muscle...
New findings:
What is the central question of this study? Resolving the mechanism(s) leading to glucose transporter 4 (GLUT4) translocation to the muscle surface membrane has great therapeutic potential. However, the measurement of GLUT4 translocation is technically challenging. Here, we asked whether electroporation of GLUT4-7myc-GFP into skeleta...
Reactive oxygen species (ROS) act as intracellular compartmentalized second messengers mediating metabolic stress-adaptation. In skeletal muscle fibers, ROS have been suggested to stimulate glucose transporter 4 (GLUT4)-dependent glucose transport during artificially evoked contraction ex vivo but whether myocellular ROS production is stimulated by...
Botulinum toxin A (botox) is a toxin used for spasticity treatment and cosmetic purposes. Botox blocks the excitation of skeletal muscle fibers by preventing the release of acetylcholine from motor nerves, a process termed chemical denervation. Surgical denervation is associated with increased expression of the canonical insulin-activated kinase Ak...
Introduction: Volume and intensity are major variables governing exercise training–mediated beneficial effects in both athletes and patients. Although polarized endurance training optimizes and maximizes physiological gains in highly trained individuals, its cardiometabolic protective-effects have not been established. The purpose of the present si...
Objective:
Chronic ad libitum low protein-high carbohydrate diet (LPHC) increases health- and life-span in mice. A periodized (p) LPHC regimen would be a more practical long-term human lifestyle intervention, but the metabolic benefits of pLPHC are not known. Also, the interactions between LPHC diet and exercise training have not been investigated...
A low‐protein high carbohydrate (LPHC) diet and a high‐protein low carbohydrate (HPLC) diet have been reported to positively and negatively regulate whole‐body glucose tolerance and insulin sensitivity, respectively. Skeletal muscle is quantitatively the most important tissue clearing glucose in the postprandial state, but it is unclear if LPHC and...
Skeletal muscle is described as an endocrine organ, constitutively or intermittently secreting bioactive molecules. The signaling pathways by which these molecules mediate changes in skeletal muscle and regulate interorgan crosstalk are only partly understood. Lactate is widely described as a signaling molecule in different cells, but the role of l...
Reactive oxygen species (ROS) are increasingly recognized as key regulators of cellular metabolism. In skeletal muscle, ROS has been linked to glucose transport in isolated electrically stimulated muscles but the exact source of ROS in the context of in vivo exercise and whether it controls in vivo glucose uptake by glucose transporter 4 (GLUT4) is...
Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the β-actin isoform which, in many cell types, is the main actin isoform. However, it is not clear that β-actin plays such a role in mature skeletal muscle. Neither dependency of glucose...
The prevalence of overweight and obesity is increasing, creating a public health problem. The loss of approximately 10% of body weight is recommended to reduce the risk of mortality associated with metabolic diseases and to increase the quality of life in adults with overweight or obesity. Non-pharmacological strategies used for weight management a...
Reactive oxygen species (ROS) participate as signaling molecules in response to exercise in skeletal muscle. However, the source of ROS and the molecular mechanisms involved in these phenomena are still not completely understood. The aim of this work was to study the role of skeletal muscle NADPH oxidase isoform 2 (NOX2) in the molecular response t...
Introduction:
The aim of this study was to determine whether whole body periodic acceleration (pGz) could improve muscle recovery after unaccustomed eccentric exercise (EE).
Methods:
Downhill treadmill running was used to elicit EE-induced muscle damage in mice, and pGz treatment (480 cycles per minute, 1 h/day) was applied daily for 10 days fol...
Hyperbaric oxygen (HBO2) exposure is a common practice used in sport medicine to accelerates recovery after injuries. However, the effect of training under HBO2 conditions in oxidative stress and physical capacity are largely unknown. The aim of the present study was to determine the effects of three weeks of HBO2 training on oxidative stress marke...
In a randomised controlled trial design, effects of six weeks of plyometric training on maximal-intensity exercise and endurance performance were compared in men and women soccer players. Young (age 21.1 ± 2.7 y) players with similar training load and competitive background were assigned to training (women, n = 19; men, n = 21) and control (women,...
Duchenne Muscular Dystrophy (DMD) is a fatal X-linked genetic disease, caused by mutations in the dystrophin gene, which cause functional loss of this protein. DMD pathology is associated with an increased production of reactive oxygen and nitrogen species (ROS and RNS). The aim of this work was to study the alterations in NF-κB activation and Inte...
Human performance efficiency and effectiveness in different sports depends to a large extent on the size, weight and proportion of the physique of the athlete. The aim of this study was to identify morphological characteristics of Brazilian Jiu-Jitsu (BJJ) wrestlers. The sample consisted of 25 highly trained male wrestlers who were separated accord...
Dehydration has long been shown to reduce physical performance, cognitive function,
and alertness in a range of athletic and non-athletic populations. The motor sport needs
several perceptive and neuromuscular skills to adequately perform the race.
Objectives.—Describe the hydration practices and dehydration prevalence in elite motor sport
athletes...
The purpose of the study was to compare the effects of progressive volume-based overload to constant volume-based overload on muscle explosive and endurance performance adaptations during a bi-weekly short-term (i.e. six weeks) plyometric training intervention in young soccer players. Three groups of young soccer players (age 13.0 +/- 2.3 y) were d...
Our aim was to compare the effects of 6-weeks of vertical, horizontal, or combined vertical and horizontal plyometric training on muscle explosive, endurance and balance performance. Forty young soccer players between 10 to 14 y of age were randomly divided into: control (CG; n = 10), vertical plyometric group (VG; n = 10), horizontal plyometric gr...
Ramírez-Campillo, R, Meylan, C, Álvarez, C, Henríquez-Olguín, C, Martínez, C, Cañas-Jamett, R, Andrade, DC, and Izquierdo, M. Effects of in-season low-volume high-intensity plyometric training on explosive actions and endurance of young soccer players. J Strength Cond Res 28(5): 1335-1342, 2014-Integrating specific training methods to improve explo...
The aim of the study was to compare the effects of plyometric training using 30, 60, or 120 s of rest between sets on explosive adaptations in young soccer players. Four groups of athletes (age 10.4 ± 2.3 y; soccer experience 3.3 ± 1.5 y) were randomly formed: control (CG; n = 15), plyometric training with 30 s (G30; n = 13), 60 s (G60; n = 14), an...
Duchenne muscular dystrophy (DMD) is a common genetic disorder characterized by a severe muscle wasting caused by the absence of dystrophin. In mdx muscle fibers, we have shown that basal ATP release is increased and that high extracellular ATP is a pro‐apoptotic stimuli. We also have shown that Dihydropyridine receptors (DHPR) are needed for ATP r...
Duchenne muscular dystrophy (DMD) is a common genetic disorder characterized by chronic inflammation and severe muscle wasting caused by the absence of dystrophin. In mdx muscle fibers, we have shown that basal ATP release was increased and that extracellular ATP stimulation is pro-apoptotic. In normal fibers, ATP release is blocked by nifedipine l...
Duchenne Muscular Dystrophy (DMD) is a recessive X-linked genetic disease, caused by mutations in the gene encoding dystrophin. DMD is characterized in humans and in mdx mice by a severe and progressive destruction of muscle fibers, inflammation, oxidative/nitrosative stress, and cell death. In mdx muscle fibers, we have shown that basal ATP releas...
Background: High intensity training could be an effective way of improving health on individuals at high metabolic risk. Aim: To investigate the effects of a high intensity training intervention on metabolic-related markers in sedentary women at high metabolic risk. Material and Methods: Forty six sedentary women with a body mass index (BMI) over 2...
The purpose of this study was to examine the effects of a localized muscle endurance resistance training program on total body and regional tissue composition. Seven men and four women (23±1 years of age) trained with their non-dominant leg during 12 weeks, three sessions per week. Each session consisted of 1 set of 960-1,200 rep (leg press exercis...
The purpose of this study was to examine the effect of a short-term plyometric training program on explosive-strength and endurance performance in highly competitive middle and long distance runners. Athletes were randomly assigned to a control group (CG, n=18, twelve men) and an explosive-strength training group (TG, n=18, ten men). Drop jump (DJ)...
In skeletal muscle cells, membrane depolarization increases reactive oxygen species (ROS) due to NOX2 activation; this is related with changes in gene expression. Our aim was to study IL‐6 gene in wt and mdx muscle cells, and its relationship with NOX2 and NF‐kB activity. Differentiated wt and mdx myotubes were stimulated with 250p, 0.5 ms at 20 Hz...
El presente estudio pretende describir el somatotipo del futbolista profesional chileno, así como determinar la variabilidad existente en el somatotipo por posición de juego. Cien jugadores profesionales varones (edad 23±4,4 años), participantes del campeonato nacional de fútbol chileno fueron incluidos en el estudio. Se realizó la medición de 10 v...
The purpose of this study was to determine the effects of short-term plyometric training interposed with 24 hours or 48 hours of rest between training sessions on explosive and endurance adaptations in young soccer players. A total of 166 players, between 10 and 17 years of age were randomly divided into 3 groups: control (CG; n=55), plyometric tra...
ABSTRACT: The objective of this study was to establish differences in vagal reactivation, through heart rate recovery and heart rate variability post exercise, in Brazilian jiu-jitsu wrestlers (BJJW). A total of 18 male athletes were evaluated, ten highly trained (HT) and eight moderately trained (MT), who performed a maximum incremental test. At t...
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by dystrophin mutations, characterized by chronic inflammation and severe muscle wasting. Dystrophic muscles exhibit activated immune cell infiltrates, up-regulated inflammatory gene expression, and increased NF-κB activity, but the contribution of the skeletal muscle cell to this proce...
The aim of this work was to study the VO2 kinetics with non-linear analysis and its relation with rowing performance.
Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by severe muscle wasting. Dystrophic muscles exhibit activated immune cell infiltrates with up-regulated inflammatory gene expression and increased NF-κB activity, but the contribution of the skeletal muscle cell to this process has been unclear. The aim of this work was to study...