Patrick Schrauwen's research while affiliated with Maastricht Universitair Medisch Centrum and other places

Publications (406)

Article
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Branched-chain amino acid (BCAA) catabolism has been considered to have an emerging role in the pathogenesis of metabolic disturbances in obesity and type 2 diabetes (T2D). Several studies showed elevated plasma BCAA levels in humans with insulin resistance and patients with T2D, although the underlying reason is unknown. Dysfunctional BCAA catabol...
Article
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Aims/hypothesis Time-restricted eating (TRE) is suggested to improve metabolic health by limiting food intake to a defined time window, thereby prolonging the overnight fast. This prolonged fast is expected to lead to a more pronounced depletion of hepatic glycogen stores overnight and might improve insulin sensitivity due to an increased need to r...
Article
Context During an asymptomatic pre-diabetic state, the functional ß-cell mass decreases up to a critical threshold triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass. Objective Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-an...
Article
Purpose of review: The rise in fructose consumption in parallel with the current epidemic of obesity and related cardiometabolic disease requires a better understanding of the pathophysiological pathways that are involved. Recent findings: Animal studies have shown that fructose has various effects on the intestines that subsequently affect intr...
Article
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Elevations in plasma branched-chain amino acid (BCAA) levels associate with insulin resistance and type 2 diabetes (T2D). Pre-clinical models suggest that lowering BCAA levels improve glucose tolerance, but data in humans are lacking. Here, we used sodium phenylbutyrate (NaPB), an accelerator of BCAA catabolism, as tool to lower plasma BCAA levels...
Article
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Aims/hypothesis In our modern society, artificial light is available around the clock and most people expose themselves to electrical light and light-emissive screens during the dark period of the natural light/dark cycle. Such suboptimal lighting conditions have been associated with adverse metabolic effects, and redesigning indoor lighting condit...
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Skeletal muscle is greatly affected by aging, resulting in a loss of metabolic and physical function. However, the underlying molecular processes and how (lack of) physical activity is involved in age-related metabolic decline in muscle function in humans is largely unknown. Here, we compared, in a cross-sectional study, the muscle metabolome from...
Article
Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoro...
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Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆)...
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Aims/hypothesis In our current society sedentary behaviour predominates in most people and is associated with the risk of developing type 2 diabetes. It has been suggested that replacing sitting time by standing and walking could be beneficial for individuals with type 2 diabetes but the underlying mechanisms are unknown and direct comparisons with...
Article
Intramyocellular lipid (IMCL) content is an energy source during acute exercise. Non-esterified fatty acid (NEFA) levels can compete with IMCL utilization during exercise. IMCL content is stored as lipid droplets (LDs) that vary in size, number, subcellular distribution and in coating with LD protein PLIN5. Little is known about how these factors a...
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The relationship between the age-associated decline in mitochondrial function and its effect on skeletal muscle physiology and function remain unclear. In the current study, we examined to what extent physical activity contributes to the decline in mitochondrial function and muscle health during aging and compared mitochondrial function in young an...
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Aims To evaluate whether the association between plasma branched-chain amino acids (BCAA) and intrahepatic lipid (IHL) was affected by physical activity level. Furthermore, to investigate if a conventional exercise training program, a subcategory of physical activity, could lower plasma BCAA along with alterations in IHL content in patients with ty...
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Background Boosting NAD+ via supplementation with niacin equivalents has been proposed as a potential modality capable of promoting healthy aging and negating age-dependent declines of skeletal muscle mass and function. Objectives We investigated the efficacy of NAD+-precursor supplementation (tryptophan, nicotinic acid, and nicotinamide) on skele...
Preprint
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Objectives The objective of the study was to validate PCr/ATP ratios as an in vivo marker for cardiac mitochondrial function. Background Cardiac energy status, measured as PCr/ATP ratio with ³¹P-MRS in vivo, was shown to be a prognostic factor in heart failure and is lowered in cardiometabolic disease. As mitochondrial function is also hampered in...
Article
Objective: SGTL2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes. The underlying mechanism may involve caloric restriction-like metabolic effects due to urinary glucose loss. We investigated the effects of dapagliflozin on 24-h energy metabolism and insulin sensitivity in patients with...
Article
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Mild cold acclimation for 10 days has been previously shown to markedly improve insulin sensitivity in patients with type 2 diabetes. Here we show in a single-arm intervention study (Trialregister.nl ID: NL4469/NTR5711) in nine patients with type 2 diabetes that ten days of mild cold acclimation (16–17 °C) in which observable, overt shivering was p...
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Objective Obesity and liver fat are associated with decreased levels of serum sex hormone‐binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. Design A cross‐sectional study...
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Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity a...
Article
Context: Elevating NAD+ levels systemically improves metabolic health, which can be accomplished via nicotinamide riboside (NR). Previously, it was demonstrated that NR supplementation in high fat diet (HFD)-fed mice decreased weight gain, normalized glucose metabolism and enhanced cold tolerance. Objective: As brown adipose tissue (BAT) is a ma...
Article
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Creatine availability in adipose tissue has been shown to have profound effects on thermogenesis and energy balance in mice. However, whether dietary creatine supplementation affects brown adipose tissue (BAT) activation in humans is unclear. In the present study, we report the results of a double-blind, randomized, placebo-controlled, cross-over t...
Article
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In non-athletes, insulin sensitivity correlates negatively with intramyocellular lipid (IMCL) content. In athletes, however, a pattern of benign IMCL storage exists, which is characterized by lipid storage in type I muscle fibres, in small and numerous lipid droplets (LDs) preferable coated with PLIN5, without affecting insulin sensitivity. Adminis...
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The circadian clock and metabolism are tightly intertwined. Hence, the specific timing of interventions that target metabolic changes may affect their efficacy. Here we retrospectively compared the metabolic health effects of morning versus afternoon exercise training in metabolically compromised subjects enrolled in a 12-week exercise training pro...
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Background Type 2 diabetes is a syndrome defined by hyperglycaemia that is the result of various degrees of pancreatic β-cell failure and reduced insulin sensitivity. Despite the fact that diabetes can be caused by multiple metabolic dysfunctions, the majority of patients are defined as having either type 1 or type 2 diabetes. Recently, Ahlqvist an...
Article
Various metabolic processes in the body oscillate throughout the natural day, driven by a biological clock. Circadian rhythms are also influenced by time cues from the environment (light exposure) and behaviour (eating and exercise). Recent evidence from diurnal- and circadian-rhythm studies indicates rhythmicity in various circulating metabolites,...
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Purpose of review: Nonalcoholic fatty liver is the result of an imbalance between lipid storage [from meal, de novo lipogenesis (DNL) and fatty acid (FA) uptake] and disposal (oxidation and VLDL output). Knowledge on the contribution of each of these pathways to liver fat content in humans is essential to develop tailored strategies to prevent and...
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Background Current dietary recommendations for cardiovascular disease (CVD) prevention focus more on dietary patterns than on single nutrients. However, randomized controlled trials using whole-diet approaches to study effects on both fasting and postprandial CVD risk markers are limited. Objective This randomized parallel trial compared the effec...
Article
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In many different cell types neutral lipids can be stored in lipid droplets (LDs). Nowadays, LDs are viewed as dynamic organelles, which store and release fatty acids depending on energy demand (LD dynamics). Proteins like perilipin 2 (PLIN2) and PLIN5 decorate the LD membrane and are determinants of LD lipolysis and fat oxidation, thus affecting L...
Article
Muscle glycogen use and glucose uptake during cold exposure increases with shivering intensity. We hypothesized that cold exposure, with shivering, would subsequently increase glucose tolerance. Fifteen healthy men (age 26 ± 5 years, body mass index 23.9 ± 2.5 kg m ⁻² ) completed two experimental trials after an overnight fast. Cold exposure (10°C)...
Article
Dietary macronutrient composition may affect hepatic liver content and its associated diseases, but the results from human intervention trials have been equivocal or underpowered. We aimed to assess the effects of dietary macronutrient composition on liver fat content by conducting a systematic review and meta-analysis of randomized controlled tria...
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Context: Patients with type 2 diabetes (T2DM) have elevated plasma branched-chain amino acid levels (BCAA). The underlying cause is however not known. Low mitochondrial oxidation of BCAA could contribute to higher plasma BCAA levels. Objective: We aimed to investigate ex vivo muscle mitochondrial oxidative capacity and in vivo BCAA oxidation mea...
Article
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Background: Low carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion...
Article
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Background: Cold acclimation and exercise training were previously shown to increase peripheral insulin sensitivity in human volunteers with type 2 diabetes. Although cold is a potent activator of brown adipose tissue, the increase in peripheral insulin sensitivity by cold is largely mediated by events occurring in skeletal muscle and at least par...
Article
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Fatty acids are an important energy source during exercise. Training status and substrate availability are determinants of the relative and absolute contribution of fatty acids and glucose to total energy expenditure. Endurance-trained athletes have a high oxidative capacity, while, in insulin-resistant individuals, fat oxidation is compromised. Fa...
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Purpose Lowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabo...
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Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and pressure in mammals. It is still unclear whether ANP controls cold-induced thermogenesis in vivo. Here, we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses half of col...
Article
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Objective Skeletal muscle mitochondrial function and energy metabolism displays day-night rhythmicity in healthy, young individuals. 24-h rhythmicity of metabolism has been implicated in the etiology of age-related metabolic disorders. Whether day-night rhythmicity in skeletal muscle mitochondrial function and energy metabolism is altered in older,...
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Background: Effects of resveratrol on metabolic health have been studied in several short-term human clinical trials, with conflicting results. Next to dose, the duration of the clinical trials may explain the lack of effect in some studies, but long-term studies are still limited. Objectives: The objective of this study was to investigate the e...
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Aims/hypothesis: Physical inactivity, low mitochondrial function, increased intramyocellular lipid (IMCL) deposition and reduced insulin sensitivity are common denominators of chronic metabolic disorders, like obesity and type 2 diabetes. Yet, whether low mitochondrial function predisposes to insulin resistance in humans is still unknown. Methods...
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Objective Exercise has been shown to improve cardiometabolic health, yet neither the molecular connection nor the effects of exercise timing have been elucidated. The aim of this study was to investigate whether ad libitum or time‐restricted mild exercise reduces atherosclerosis development in atherosclerosis‐prone dyslipidemic APOE*3‐Leiden.CETP m...
Article
To be prepared for alternating metabolic demands occurring over the 24‐hour day, the body preserves information on time in skeletal muscle, and in all cells, through a circadian‐clock mechanism. Skeletal muscle can be considered the largest collection of peripheral clocks in the body, with a major contribution to whole‐body energy metabolism. Compa...
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Aim Heat exposure has been indicated to positively affect glucose metabolism. An involvement of heat shock protein 72 (HSP72) in the enhancement of insulin sensitivity upon heat exposure has been previously suggested. Here, we performed an intervention study exploring the effect of passive heat acclimation (PHA) on glucose metabolism and intracellu...
Article
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Diurnal oscillations in energy metabolism are linked to the activity of biological clocks and contribute to whole‐body glucose homeostasis. Postprandially, skeletal muscle takes up approximately 80% of circulatory glucose and hence is a key organ in maintenance of glucose homeostasis. Dysregulation of molecular clock components in skeletal muscle d...
Article
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Background: Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. Objectives: We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health para...
Article
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Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study desi...
Article
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Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1)...
Article
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Objective Human energy metabolism is under the regulation of the molecular circadian clock; we recently reported that mitochondrial respiration displays a day-night rhythm under study conditions that are similar to real life. Mitochondria are interconnected with lipid droplets, which are of importance in fuel utilization and play a role in muscle i...
Preprint
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Atrial natriuretic peptide (ANP) is a cardiac hormone controlling blood volume and arterial pressure in mammals. It is unclear whether and how ANP controls cold-induced thermogenesis in vivo. Here we show that acute cold exposure induces cardiac ANP secretion in mice and humans. Genetic inactivation of ANP promotes cold intolerance and suppresses a...
Article
Background & aims: Metabolic flexibility is the ability to adapt fuel oxidation to fuel availability. Metabolic inflexibility has been associated with obesity, the metabolic syndrome and insulin resistance, and can be improved by exercise or weight loss. Dietary changes can modulate metabolic flexibility; however, the effect of a whole diet approa...
Article
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BACKGROUND Insulin resistance results from impaired skeletal muscle glucose transport/phosphorylation, linked to augmented lipid availability. Despite greater intramuscular lipids, athletes are highly insulin sensitive, which could result from higher rates of insulin-stimulated glycogen synthesis or glucose transport/phosphorylation and oxidation....
Article
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Background: Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibili...
Article
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Purpose We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT). Methods Ten thyroid carcinoma patients underwent an ¹⁸F-FDG PET/CT during post-thyroidectomy...
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NAD⁺ has gone in and out of fashion within the scientific community a number of times since its discovery in the early 1900s. Over the last decade, NAD⁺ has emerged as a potential target for combatting metabolic disturbances and the mitochondrial dysfunction that is mediated through sirtuin (SIRT) enzymes. The beneficial metabolic effects of the NA...
Poster
Synopsis Non-alcoholic fatty liver (NAFL) has become a major threat to metabolic health. Animal studies have suggested that disturbances in choline metabolism may be linked to the development of NAFL. However, to date, human data on the link of choline and NAFL is scarce. The trimethylammonium (TMA) group of choline can be detected with H-MRS at 3....
Poster
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1H-MRS is extensively used to measure the hepatic lipid content. Conventionally, the water resonance is used as an internal reference, thereby assuming a constant T decay of water across individuals to estimate absolute hepatic lipid content. However, the T values reported in literature for 3T vary widely, which might be due to different subject po...