Mariëlle P K J Engelen

• PhD
• Managing Director at Texas A&M University

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. In this pilot study, we studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel i...

Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia’s toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to inves...

Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gl...

Human sepsis is characterized by increased protein breakdown and changes in arginine and citrulline metabolism. However, it is unclear whether this is caused by changes in transorgan metabolism. We therefore studied in a Pseudomonas aeruginosa induced pig sepsis model the changes in protein and arginine related metabolism on whole body (Wb) and tra...

Purpose of review This study aimed to discuss the use of the pulse stable isotope tracer approach to study changes in metabolism in healthy individuals and critically ill patients. Recent findings and conclusion We found that in the postabsorptive state and healthy condition, intracellular protein breakdown and net intracellular protein breakdown,...

Purpose of review Stable isotope methods have been used for many years to assess whole body protein and amino acid kinetics in critically ill patients. In recent years, new isotope approaches and tracer insights have been developed. The tracer pulse approach has some advantages above the established primed-continuous tracer infusion approach becaus...

Background & aims: Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature...

Background: Sarcopenia, or skeletal muscle loss, is common complication in COPD and contributes to adverse clinical outcomes including mortality. As the disease progresses, a significant proportion of COPD patients develop nocturnal hypoxemia which causes tissue-level hypoxia in the skeletal muscle which we have termed prolonged intermittent hypoxi...

Abnormalities pertaining to glycoconjugates (glycoproteins, proteoglycans, and glycolipids) of the neural extracellular matrix have been identified as a susceptibility factor in autism spectrum disorder. We studied the urine excretion of sulfated glycosaminoglycans in children with autism spectrum disorder (n=61), in comparison to age- and sex-matc...

Children with autism spectrum disorder may exhibit nutritional deficiencies due to reduced intake, genetic variants, autoantibodies interfering with vitamin transport, and the accumulation of toxic compounds that consume vitamins. Importantly, vitamins and metal ions are essential for several metabolic pathways and for neurotransmitter functioning....

Background: The trajectory from healthy to critical illness is influenced by numerous factors, including metabolism, which differs substantially between males and females. Whole body protein breakdown is substantially increased in critically ill patients, but it remains unclear whether there are sex differences that could explain the different hea...

Background: Production rates of the short-chain fatty acids (SCFA) acetate, propionate, and butyrate, which are beneficial metabolites of the intestinal microbiota, are difficult to measure in humans due to inaccessibility of the intestine to perform measurements, and the high first-pass metabolism of SCFAs in colonocytes and liver. We developed a...

Background Abdominal obesity (AO) is linked to reduced health status and mortality. While it is known that AO is prevalent in chronic obstructive pulmonary disease (AO-COPD), the specific metabolic and functional consequences associated with AO-COPD remain understudied. Methods We studied 199 older adults with COPD and 168 control subjects with an...

Background β−hydroxy-β−methylbutyrate (HMB) might improve muscle function and maintain its mass in critically ill patients. We aimed to investigate whether the administration of HMB influenced the plasma levels of growth hormone (GH)/insulin-like growth factor-1 (IGF-1), C-peptide, and 25-OH vitamin-D. Methods Post-hoc analysis of the study HMB-IC...

Background There is growing interest in the supplementation of arginine (Arg) and citrulline (Cit) in obesity due to their potential anti-obesogenic and anti-inflammatory properties. However, there is no consensus on the metabolic changes in Arg kinetics in obesity. Objective This exploratory cross-sectional study aimed to investigate the associat...

Background: Chronic disease causes skeletal muscle loss that contributes to morbidity and mortality. There are limited data on the impact of dynamic muscle loss on clinical outcomes in COVID-19. We hypothesized that acute COVID-19-related muscle loss (acute sarcopenia) is associated with adverse outcomes. Methods: A retrospective analysis of a p...

Background Disturbances in protein metabolism and impaired muscle health have been observed in chronic obstructive pulmonary disease (COPD). The ω-3 (n–3) PUFAs EPA and DHA are known for their anti-inflammatory and muscle health-enhancing properties. Objectives We examined whether daily EPA + DHA supplementation can improve daily protein homeostas...

Background & aims Postabsorptive whole body protein kinetics are related to age, gender, body mass index (BMI), and habitual protein intake level. It is unclear how protein synthesis, breakdown, and postabsorptive protein balance rates are affected in Chronic Obstructive Pulmonary Disease (COPD)) and whether these relate to disease severity, lifest...

Purpose of review: The branched-chain amino acids (BCAA), branched-chain keto acids (BCKA), and β-hydroxy β-methylbutyric acid (HMB) have regained interest as food ingredients in health and disease. To support nutritional strategies, it is critical to gain insight into the whole body and transorgan kinetics of these components. We, therefore, revi...

Background: Depression is one of the most common and untreated comorbidities in chronic obstructive pulmonary disease (COPD), and is associated with poor health outcomes (e.g. increased hospitalization/exacerbation rates). Although metabolic disturbances have been suggested in depressed non-diseased conditions, comprehensive metabolic phenotyping...

This opinion paper presents a short review of the potential impact of protein on muscle anabolism in cancer, which is associated with better patient outcomes. Protein source is a topic of interest for patients and clinicians, partly due to recent emphasis on the supposed non-beneficial effect of proteins; therefore, misconceptions involving animal-...

The short-chain fatty acids (SCFAs) acetate, propionate, butyrate, isovalerate, and valerate are end products of intestinal bacterial fermentation and important mediators in the interplay between the intestine and peripheral organs. To unravel the transorgan fluxes and mass balance comparisons of SCFAs, we measured their net fluxes across several o...

Background The amount of the macronutrients protein and carbohydrate (CHO) in a mixed meal is known to affect each other's digestion, absorption, and subsequent metabolism. While the effect of the amount of dietary protein and fat on the glycemic response is well studied, the ability of postprandial plasma amino acid patterns to predict the meal co...

Purpose Muscle wasting deteriorates life quality after critical illness and increases mortality. Wasting starts upon admission to intensive care unit (ICU). We aimed to determine whether β−hydroxy-β−methylbutyrate (HMB), a metabolite of leucine, can attenuate this process. Methods Prospective randomized, placebo-controlled double blind trial. Incl...

Purpose of review: This review will discuss recent studies showing that patients with chronic wasting diseases suffer from a variety of small intestinal impairments which might negatively impact the colonic microbiota and overall well-being. New insights will be addressed as well as novel approaches to assess intestinal function. Recent findings:...

Objectives Many obese subjects have a lower muscle performance. Short-chain fatty acids (SCFAs; acetate, propionate, butyrate, valerate, and isovalerate) are derived from microbial fermentation of dietary fiber and are metabolic fuels for skeletal muscle during periods of sustained contraction. We compared plasma SCFA concentrations between obese a...

Objectives Recent studies suggest that glutamate (GLU) signaling abnormalities are involved in the etiology of Autism Spectrum Disorder (ASD), suggesting perturbations in GLU and glutamine (GLN) metabolism. Although GLU and GLN plasma concentrations have been linked to cognitive decline, the actual production of GLU and GLN have never been measured...

Objectives Cancer patients were shown to have an altered intestinal microbiota composition and lower fecal concentrations of the bacterial metabolites short-chain fatty acids (SCFA), which among others serve as energy source to muscle. We previously described an association between reduced plasma SCFA concentrations and muscle dysfunction in chroni...

Background: Small and large intestinal perturbations have been described as prevalent extracardiac systemic manifestations in Congestive Heart Failure (CHF) but alterations in protein digestion and absorption and plasma short-chain fatty acid concentrations (SCFA), and the potential link with other systemic effects (e.g. lower muscle and cognitive...

Introduction Reduced skeletal muscle function and cognitive performance are common extrapulmonary features in Chronic Obstructive Pulmonary Disease (COPD) but their connection remains unclear. Whether presence or absence of skeletal muscle dysfunction in COPD patients is linked to a specific phenotype consisting of reduced cognitive performance, co...

Patients with advanced chronic obstructive pulmonary disease (COPD) develop skeletal muscle loss (sarcopenia) that is associated with adverse clinical outcomes including mortality. We evaluated if thoracic muscle area is associated with clinical outcomes in patients with severe COPD. We analyzed consecutive patients with severe COPD undergoing eval...

There are multiple lines of evidence for an impaired sulfur amino acid (SAA) metabolism in autism spectrum disorder (ASD). For instance, the concentrations of methionine, cysteine and S-adenosylmethionine (SAM) in body fluids of individuals with ASD is significantly lower while the concentration of S-adenosylhomocysteine (SAH) is significantly high...

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision of when and in which protein and AA composition to deliver in ICU, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patie...

[This corrects the article DOI: 10.1371/journal.pone.0242926.].

Objective: Branched-chain amino acids (BCAA) and their metabolites the branched-chain keto acids (BCKA) and β-Hydroxy β-methylbutyric acid (HMB) are involved in the regulation of key signaling pathways in the anabolic response to a meal. However, their (inter)organ kinetics remain unclear. Therefore, BCAA (leucine (LEU), valine (VAL), isoleucine (...

With the rise in physical inactivity and its related diseases, it is necessary to understand the mechanisms involved in physical activity regulation. Biological factors regulating physical activity are studied to establish a possible target for improving the physical activity level. However, little is known about the role metabolism plays in physic...

Purpose: Gut symptoms and markers of gut dysfunction have been observed in patients with Chronic Obstructive Pulmonary disease (COPD). It remains unclear whether walking exercise induces disturbances in protein digestion and amino acid absorption and whole body protein kinetics in these subjects due to exercise induced hypoxia. Methods: Sixteen...

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of...

Background & aims Gastrointestinal symptoms are prevalent extrapulmonary systemic manifestations of Chronic Obstructive Pulmonary Disease (COPD), but have been rarely studied. We dissected the perturbations in intestinal function in human patients with COPD using comprehensive metabolic and physiological approaches. Methods In this observational s...

Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), orni...

Aims Gastrointestinal symptoms are common during chemotherapy, but underlying disturbances in gut function and impact on daily life are unclear. This study investigates gut function in a heterogenous group of cancer patients with gastrointestinal symptoms during chemotherapy, and the relation with anabolic response, muscle health, and daily functio...

Objectives Patients with congestive heart failure (CHF) frequently suffer from cognitive deficits and depressive symptoms. Changes in intestinal microbiota composition have been suggested to promote those features in CHF via alterations in their metabolite release. We examined the association between reduced psychological well-being (including cogn...

Objectives The short-chain fatty acids (SCFA) acetate (C2), propionate (C3), butyrate (C4), isovalerate (Ci5), and valerate (C5) are endproducts of anaerobic fermentation by the intestinal microbiota and known to play a crucial role as energy source for colonocytes (C2 and C4) and muscle (C2), and as mediators in signaling pathways. To unravel the...

Objectives Optimal feeding in patients recovering from sepsis is critical to preserve muscle mass. In sepsis, glutamine (Gln) is considered a conditional essential amino acid and low plasma level of its precursor glutamate (Glu), is associated with higher mortality. An essential amino acid (EAA) mixture restores protein anabolism in the early recov...

Objectives Aging is associated with changes in body composition (eg. sarcopenia) but the overall effects of aging on systemic amino acid kinetics need further exploration. We previously reported metabolic differences in certain amino acids between young and older adults using comprehensive metabolic flux analysis. We expanded this novel single stab...

Objectives Very Low-Calorie Diet (VLCD) is an approved method to safely achieve substantial short-term weight loss in obese patients. We previously reported that two weeks of the VLCD maintains whole-body protein and amino acid turnover despite a large reduction in lean body mass. Since the observed effects on body weight (BW) and composition diffe...