Daniela Tavian

Mutations in the PNPLA2 gene, which encodes adipose triglyceride lipase (ATGL), are linked to neutral lipid storage disease with myopathy (NLSDM). This rare genetic disorder is marked by abnormal accumulation of neutral lipids in cytoplasmic lipid droplets, leading to muscle-related symptoms such as weakness, cramps and progressive myopathy in almost all patients, and cardiomyopathy in about half of the patients. Here, we report a novel PNPLA2 variant and the clinical and MRI findings of a 42-year-old Italian male with NLSDM, revealing a myopathic pattern involving both proximal and distal muscles of all four limbs, as well as axial and facial muscles, without detectable cardiac abnormalities. Genetic testing uncovered a novel PNPLA2 homozygous mutation, resulting in the deletion of a single amino acid in the first ATGL LC3-interacting region (LIR) motif. In addition, bioinformatic analyses predicted changes in mutated ATGL’s structure that could affect its enzymatic function and impair both lipolysis and lipophagy by disrupting ATGL-LC3 interaction. Western blot analysis confirmed a block in lipophagic flux. This study broadens our understanding of the genetic and clinical heterogeneity of NLSDM, highlighting the complexity of the disease.

Physical training is widely recognised for its capacity to acutely reduce anxiety, enhance mood, and foster psychological resilience. Indeed, robust evidence within the broader exercise-mental heal...

Background: Adiponectin is an adipokine with insulin-sensitizing, anti-inflammatory, and cytoprotective properties that also plays a key role in metabolic adaptation to exercise. Although its regulation after resistance exercise has been extensively documented, less is known about its short-term modulation and its correlation with muscle damage markers following resistance training. Methods: Nine resistance-trained young men completed two sessions of total-body resistance exercise: (1) high time under tension (TUT) (5-1-2-1 cadence, to failure; ETS1) and (2) moderate TUT (2-1-2-1 cadence, two repetitions in reserve; ETS2). Plasma and saliva samples were collected before exercise and at 15 min, 24 h, and 48 h after exercise to assess total adiponectin by ELISA. Plasma creatine kinase (CK) and a Visual Analog Scale (VAS) were also measured for muscle soreness. Results: Plasma adiponectin significantly decreased from baseline to 48 h post-exercise in both sessions (p < 0.001), with no differences between the TUT conditions. Salivary adiponectin remained unchanged. Although a significant increase in CK and a decrease in adiponectin were observed at the group level, correlation analysis revealed no significant linear relationship between the magnitude of CK elevation and adiponectin reduction. Conclusions: Overall, these findings support the role of adiponectin as a marker of acute metabolic adaptation to resistance exercise. Acute resistance exercise elicited a time-dependent decrease in circulating adiponectin, irrespective of TUT. The temporal pattern of adiponectin decrease coincided with the rise in muscle damage markers, yet the lack of direct correlation suggests distinct regulatory mechanisms, while the lack of salivary changes underscores the complexity of adipokine regulation in vivo and suggests that saliva is not a reliable indicator of changes in circulating adiponectin.

Neutral Lipid Storage Disease with Myopathy (NLSDM) is a rare lipid metabolism disorder caused by impaired Adipose Triglyceride Lipase (ATGL) activity, leading to neutral lipid accumulation in various tissues. It typically manifests with progressive skeletal myopathy, with an onset of around 35 years. In addition, some patients develop cardiomyopathy and liver dysfunction. Herein, we report the molecular characterization of a 27-year-old Hungarian patient and his family in whom two severe PNPLA2 mutations led to complete loss of ATGL production in the patient’s tissues. DNA sequencing revealed a nonsense (c.24G>A) and a frameshift mutation (c.798dupC) in the PNPLA2 gene. RNA analysis showed nonsense-mediated decay of the c.798dupC transcript, while c.24G>A was normally expressed in the patient. However, Western blot analysis did not detect ATGL protein production. From a clinical perspective, our patient exhibited pes planus, proximal muscle weakness of the lower limbs and elevated CK levels from the age of six. MRI and biopsy revealed lipid accumulation, and leukocytes showed Jordans’ anomaly. The muscle weakness progressed, and cardiomyopathy and hepatic steatosis were also observed recently. The case highlights two severe PNPLA2 mutations leading to complete ATGL deficiency and an unusual early-onset myopathy in childhood.

Irisin’s response to Resistance Exercise (RE) remains unclear. We investigated plasma and salivary irisin levels following acute moderate load/high volume (ML/HV) RE and explored correlations with muscle damage markers. Eight healthy, resistance-trained young males (23.3±2.5 yrs) completed one ML/HV RE session (full-body, 30 sets to failure, 70% 1RM). Plasma/saliva irisin, plasma Creatine Kinase (CK), and Visual Analogue Scale (VAS) for muscle soreness were assessed at baseline, 15 min, 24h, and 48h post-exercise. Plasma irisin increased significantly by ~9% (p=0.01) and salivary irisin by ~4% (p=0.02) at 15 min post-exercise, returning towards baseline by 24h. A strong correlation (rho=0.8, p=0.03) existed between percentage changes in plasma and salivary irisin at 15 min. CK and VAS peaked at 24h (p<0.001; p=0.02 vs 48h, respectively), but showed no significant correlation with irisin changes. Acute ML/HV RE elicits a transient increase in plasma and salivary irisin. Saliva may be a useful non-invasive proxy for irisin changes post-RE. This acute irisin response appears independent of EIMD markers in this population. Findings require confirmation in larger studies.

BACKGROUND: Morbidity and mortality of heart failure with preserved ejection fraction (HFpEF) is increased in metabolic disorders. However, options for preventing and treating these prevalent outcomes are limited. Intramyocardial lipotoxicity contributes to cardiac dysfunction. Here, we investigate the mechanisms underlying EDEM2 (endoplasmic reticulum degradation–enhancing alpha-mannosidase–like protein 2) regulation of cardiac lipid homeostasis and assess strategies that inhibit the incidence and progression of HFpEF. METHODS: Metabolic stress was induced in C57BL/6 male mice using a high-fat diet and N ω-nitro-L-arginine methyl ester. The recombinant adeno-associated virus 9 delivery system was used for loss- and gain-of-function studies. Palmitic acid and oleic acid stimulation of rat cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes imitated a condition of high lipids in vitro. Molecular mechanisms were investigated via RNA sequencing, mass spectrometry proteomics, lipidomic analyses, transmission electron microscopy, histology, and luciferase reporter assays. RESULTS: In the human heart, we first detected lipid overload accompanied by a reduction of XBP1 (X-box binding protein 1) under metabolic stress. Thereafter, a decrease in EDEM2 was confirmed in human and mouse HFpEF hearts. Given that XBP1s (spliced X-box binding protein 1) is a transcription factor, EDEM2 was identified as its new target in cardiomyocytes. EDEM2 knockdown mice manifested lipid droplet accumulation and higher levels of triglycerides and diglycerides in the myocardium, aggravating oxidative stress, hypertrophy, and the onset and progression of HFpEF under metabolic stress. XBP1s ablation mice displayed a similar myocardial lipid disturbance and cardiac phenotypes, which were reversed by EDEM2 overexpression. Mechanistically, the findings obtained from rat cardiomyocytes and human induced pluripotent stem cell–derived cardiomyocytes demonstrated that, in the presence of EDEM2, SEC23A mediated intracellular translocation of ATGL (adipose triglyceride lipase) under fatty acid stimulation, inhibiting ATGL degradation and excessive intracellular lipid droplets. Furthermore, the functional studies supported that EDEM2 prevention of lipid overload occurred in an ATGL-dependent manner. Therapeutically, cardiac XBP1s or EDEM2 restoration mitigated lipid deposition and preserved lipid profiles in the myocardium, thus preventing the development of HFpEF. CONCLUSIONS: We demonstrate a cardioprotective mechanism regulating myocardial lipid homeostasis. The findings provide a promising therapeutic target to prevent and treat HFpEF, a condition with limited treatment options.

Purpose: This study aimed to investigate the time course of β-endorphin (β-EDP) levels in healthy males following an acute exercise, while considering their age and physical fitness (PF) level. Methods: Participants (N = 29, 20–65 years) were categorized in good PF young adult (YA1), excellent PF young adult (YA2), and excellent PF middle-aged adult (MA) group, depending on peak oxygen uptake and age. They underwent a maximal incremental cycling test, with blood samples collected at baseline (T0), 15 min (T1), and 24 h post-exercise (T2). Serum β-EDP levels were measured using an ELISA kit. Results: Significant increases in β-EDP levels were observed from T0 to T1 in all enrolled subjects. In YA1, levels rose from 170.1 to 202.5 pg/ml (p < 0.001), in YA2 from 188.4 to 230.3 pg/ml (p < 0.05), and in MA level increased from 153 to 189.3 pg/ml (p < 0.01). YA2 showed higher levels of β-EDP than MA in any time point (p < 0.05). All groups displayed a significant decrease of β-EDP from T1 to T2. Comparison between groups revealed that age significantly influenced baseline β-EDP levels, with notable differences between young and middle-aged individuals. Noteworthy, MA with excellent PF presented similar β-EDP levels to young with good PF. Conclusion: Acute exercise triggers a notable but transient elevation of serum β-EDP levels in both young and middle-aged adults, with the latter exhibiting lower baseline levels. Additionally, our findings suggest that age may have a greater influence on β-EDP secretion, both at rest and after physical exercise compared to PF level.

Medium-sized scientific conferences held in hotels large enough to accommodate all participants increase opportunities for constructive discussion during breaks, and for evenings that bring together young and senior experts of basic sciences and clinical specialties. Time for group discussions offer opportunities for new collaborations and for jobs for young researchers. Since 1991 the Padova Muscle Days have offered collaborative opportunities that have matured into innovative multidisciplinary results to the point that it came naturally for us to underline it with a neologism now included in the title of the 2025 event: "Mobility Medicine". It is a discipline which developed naturally when we brought together fragmented areas of knowledge into one meeting. The Padua Days on Muscle and Mobility Medicine 2025 (2025Pdm3) will be hosted at the Hotel Petrarca, Euganean Thermae (Padua, Italy) from 25 to 29 March 2025. The list of unique sessions within the included program and the following Collection of Abstracts testify that it is possible to organize valid countermeasures to the inevitable tendencies towards hyper-specialization that the explosive increase in scientific progress brings. The European Journal of Translational Myology and Mobility Medicine (Ejtm3) will accept typescripts on results presented at the 2025Pdm3. Furthermore, an additional option for publication of full original Articles or Reviews is the Special "New Trends in Musculoskeletal Imaging" of the MDPI Journal Diagnostics, because diagnosis is essential to manage and follow-up neuro- metabolic- muscular- disorder and the decay of performances in aging. We hope that many will share our dreams and we make them come true at the 2025 Pdm3 Conference.

Mega scientific conferences increasingly suffer from the need for short and poster presentations without discussion. An alternative is to organize workshops in hotels large enough to accommodate all participants. This significantly increases the opportunities for constructive discussion during breakfasts, lunches, dinners and long evenings that can bring together experts of scientific and clinical sub-specialties and young fellows. Time for groups' discussions and new collaborations are increased so as the job opportunities for the young researchers. The Padova Muscle Days have offered in the previous thirty-five years these opportunities, which have matured into innovative and multidisciplinary results to the point that it came naturally to underline it with a neologism now included in the title of the 2025 event: “Mobility Medicine”, a discipline not yet officially recognised, that makes explicit the call for rejoining knowledges dispersed in sub-specialisations. The included program of the Padua Days on Muscle and Mobility Medicine 2025 (2025Pdm3) will be hosted at the Hotel Petrarca in Euganean Thermae (Padua, Italy) from 25 to 29 March 2025. It further testifies by listing unique Sessions that it is possible to organize valid countermeasures to the inevitable tendencies towards hyperspecialization that the explosive increase in scientific progress brings with it. Furthermore, the European Journal of Translational Myology and Mobility Medicine (Ejtm3) will accept typescripts on results presented at the 2025Pdm3, together with the Special Section: New Trends in Musculoskeletal Imaging of the MDPI (Basel) Journal Diagnostics, because diagnosis is essential to prevent, manage and follow-up not only neuro-metabolic-muscular disorders, but the unavoidable physiologicical decay of performances in early and late aging. Hoping many others share our dreams, we look forward to meeting you at 2025Pdm3 conference.