Loss or inhibition of lysosomal acid lipase leads to cholesteryl ester accumulation without affecting muscle formation or mitochondrial function.

Skeletal muscle (SM) is essential for movement, stability, and overall body function, and it readily adapts to changes in energy demand. Myogenesis is energy-intensive and involves complex molecular and cellular events. We recently demonstrated that the absence of lysosomal acid lipase (LAL) significantly impacts the SM phenotype, primarily by disrupting energy homeostasis and reducing ATP production.

Association of Small HDL Subclasses with Mortality Risk in Chronic Kidney Disease.

High-density lipoproteins (HDL) exist in various subclasses, with smaller HDL particles possessing the highest anti-oxidative and anti-inflammatory properties. Understanding the role of these specific subclasses in chronic kidney disease (CKD) could provide valuable insights into disease progression and potential therapeutic targets. In the present study, we assessed HDL subclass composition in 463 patients with CKD stage 2-4 using nuclear magnetic resonance spectroscopy.

Probiotic Therapy of Gastrointestinal Symptoms During COVID-19 Infection: A Randomized, Double-Blind, Placebo-Controlled, Remote Study.

Background: The novel coronavirus (SARS-CoV-2) led to gastrointestinal manifestations in up to 50% of cases, with diarrhea being common, and probiotics have been suggested as a potential treatment.

Aim: This study aimed to assess changes in the microbiome and the effects of a multispecies probiotic in patients with COVID-19 in home quarantine through a fully remote telemedical approach.

Methods: Thirty patients were randomized to receive either the Ecologic AAD probiotic (Winclove Probiotics, Amsterdam, The Netherlands), on the market as OMNi-BiOTiC 10 (Allergosan, Austria), or a placebo for 30 days in a 2:1 ratio.

Alteration of the Gut-Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study.

Background: The gut-lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators.

Aim: We conducted a pilot study to understand alterations in the gut-lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease.

Methods: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut-lung axis at baseline and throughout probiotic intervention.

Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice.

Background: Dietary restriction (DR) has multiple beneficial effects on health and longevity and can also improve the efficacy of certain therapies. Diets used to instigate DR are diverse and the corresponding response is not uniformly measured. We compared the systemic and liver-specific transcriptional response to intermittent fasting (IF) and commercially available fasting-mimicking diet (FMD) after short- and long-term use in C57BL/6 J mice.

Methods to Study Structure and Dynamics of FOXO Proteins.

FOXOs are highly dynamic transcription factors consisting of one conserved DNA-binding domain (forkhead domain) as well as intrinsically disordered regions (IDRs) at the N- and C-termini. These IDRs are essential and regulate transcriptional activity of FOXOs by serving as interaction platform for cofactors. Furthermore, the IDRs are involved in intra- and intermolecular homeotypic and heterotypic interactions between FOXOs and in turn mediate FOXO auto-inhibition and condensate formation.

IGF2BP1 phosphorylation in the disordered linkers regulates ribonucleoprotein condensate formation and RNA metabolism.

The insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) is a conserved RNA-binding protein that regulates RNA stability, localization and translation. IGF2BP1 is part of various ribonucleoprotein (RNP) condensates. However, the mechanism that regulates its assembly into condensates remains unknown.

Exploring neural markers of dereification in meditation based on EEG and personalized models of electrophysiological brain states.

With mounting evidence for the benefits of meditation, there has been a growing interest in measuring and quantifying meditative states. This study introduces the Inner Dereification Index (IDI), a class of personalized models designed to quantify the distance from non-meditative states such as mind wandering based on a single individual's neural activity. In addition to demonstrating high classification accuracy (median AUC: 0.

Sex-Related Differences in the Associations between Adiponectin and Serum Lipoproteins in Healthy Subjects and Patients with Metabolic Syndrome.

The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS.

Lanifibranor Reduces Inflammation and Improves Dyslipidemia in Lysosomal Acid Lipase-Deficient Mice.

Background And Aims: Recent studies showed that patients suffering from lysosomal acid lipase deficiency (LAL-D) benefit from enzyme replacement therapy; however, liver histopathology improved in some but not all patients. We hypothesized that the pan-peroxisome proliferator-activated receptor agonist lanifibranor may have beneficial effects on liver inflammation in LAL knockout (Lal-/-) mice based on its promising results in alleviating liver inflammation in patients with metabolic dysfunction-associated steatohepatitis.

Methods: Female Lal-/- mice were daily gavaged with lanifibranor or vehicle for 21 days.

Effects of dietary interventions and intermittent fasting on HDL function in obese individuals with T2DM: a randomized controlled trial.

Background: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain.

Impaired HDL antioxidant and anti-inflammatory functions are linked to increased mortality in acute heart failure patients.

Aims: Acute heart failure (AHF) is typified by inflammatory and oxidative stress responses, which are associated with unfavorable patient outcomes. Given the anti-inflammatory and antioxidant properties of high-density lipoprotein (HDL), this study sought to examine the relationship between impaired HDL function and mortality in AHF patients. The complex interplay between various HDL-related biomarkers and clinical outcomes remains poorly understood.

Targeting organ-specific mitochondrial dysfunction to improve biological aging.

In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function.

Spermidine is essential for fasting-mediated autophagy and longevity.

Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism.

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

Background: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner.

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

Background: The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability.

Metabolic Reprogramming Is an Initial Step in Pancreatic Carcinogenesis That Can Be Targeted to Inhibit Acinar-to-Ductal Metaplasia.

Metabolic reprogramming is a hallmark of cancer and is crucial for cancer progression, making it an attractive therapeutic target. Understanding the role of metabolic reprogramming in cancer initiation could help identify prevention strategies. To address this, we investigated metabolism during acinar-to-ductal metaplasia (ADM), the first step of pancreatic carcinogenesis.

Hexokinase 1 forms rings that regulate mitochondrial fission during energy stress.

Metabolic enzymes can adapt during energy stress, but the consequences of these adaptations remain understudied. Here, we discovered that hexokinase 1 (HK1), a key glycolytic enzyme, forms rings around mitochondria during energy stress. These HK1-rings constrict mitochondria at contact sites with the endoplasmic reticulum (ER) and mitochondrial dynamics protein (MiD51).

PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression.

Introduction: An increasing body of evidence suggests a strong relationship between gut health and mental state. Lately, a connection between butyrate-producing bacteria and sleep quality has been discussed. The PROVIT study, as a randomized, double-blind, 4-week, multispecies probiotic intervention study, aims at elucidating the potential interconnection between the gut's metabolome and the molecular clock in individuals with major depressive disorder (MDD).

Millifluidic magnetophoresis-based chip for age-specific fractionation: evaluating the impact of age on metabolomics and gene expression in yeast.

A novel millifluidic process introduces age-based fractionation of var. yeast culture through magnetophoresis. yeast is a model organism for aging research used in various industries.

Serum Levels of Adiponectin Are Strongly Associated with Lipoprotein Subclasses in Healthy Volunteers but Not in Patients with Metabolic Syndrome.

Metabolic syndrome (MS) is a widespread disease in developed countries, accompanied, among others, by decreased adiponectin serum levels and perturbed lipoprotein metabolism. The associations between the serum levels of adiponectin and lipoproteins have been extensively studied in the past under healthy conditions, yet it remains unexplored whether the observed associations also exist in patients with MS. Therefore, in the present study, we analyzed the serum levels of lipoprotein subclasses using nuclear magnetic resonance spectroscopy and examined their associations with the serum levels of adiponectin in patients with MS in comparison with healthy volunteers (HVs).

Advanced Oxidation Protein Products Are Strongly Associated with the Serum Levels and Lipid Contents of Lipoprotein Subclasses in Healthy Volunteers and Patients with Metabolic Syndrome.

The association between advanced oxidation protein products (AOPPs) and lipoprotein subclasses remains unexplored. Therefore, we performed comprehensive lipoprotein profiling of serum using NMR spectroscopy and examined the associations of lipoprotein subclasses with the serum levels of AOPPs in healthy volunteers (HVs) and patients with metabolic syndrome (MS). The serum levels of AOPPs were significantly positively correlated with the serum levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL); however, they were significantly negatively correlated with high-density lipoprotein (HDL).