Search Results (547)

The integration of omics technologies, including genomics, proteomics, metabolomics, and microbiomics, has transformed sports science, particularly soccer, by providing new opportunities to optimize player performance, reduce injury risk, and enhance recovery. This systematic literature review was conducted in accordance with PRISMA 2020 guidelines and structured using the PICOS/PECOS framework. Comprehensive searches were performed in PubMed, Scopus, and Web of Science up to August 2025. Eligible studies were peer-reviewed original research involving professional or elite soccer players that applied at least one omics approach to outcomes related to performance, health, recovery, or injury prevention. Reviews, conference abstracts, editorials, and studies not involving soccer or omics technologies were excluded. A total of 139 studies met the inclusion criteria. Across the included studies, a total of 19,449 participants were analyzed. Genomic investigations identified numerous single-nucleotide polymorphisms (SNPs) spanning key biological pathways. Cardiovascular and vascular genes (e.g., ACE, AGT, NOS3, VEGF, ADRA2A, ADRB1–3) were associated with endurance, cardiovascular regulation, and recovery. Genes related to muscle structure, metabolism, and hypertrophy (e.g., ACTN3, CKM, MLCK, TRIM63, TTN-AS1, HIF1A, MSTN, MCT1, AMPD1) were linked to sprint performance, metabolic efficiency, and muscle injury susceptibility. Neurotransmission-related genes (BDNF, COMT, DRD1–3, DBH, SLC6A4, HTR2A, APOE) influenced motivation, fatigue, cognitive performance, and brain injury recovery. Connective tissue and extracellular matrix genes (COL1A1, COL1A2, COL2A1, COL5A1, COL12A1, COL22A1, ELN, EMILIN1, TNC, MMP3, GEFT, LIF, HGF) were implicated in ligament, tendon, and muscle injury risk. Energy metabolism and mitochondrial function genes (PPARA, PPARG, PPARD, PPARGC1A, UCP1–3, FTO, TFAM) shaped endurance capacity, substrate utilization, and body composition. Oxidative stress and detoxification pathways (GSTM1, GSTP1, GSTT1, NRF2) influenced recovery and resilience, while bone-related variants (VDR, P2RX7, RANK/RANKL/OPG) were associated with bone density and remodeling. Beyond genomics, proteomics identified markers of muscle damage and repair, metabolomics characterized fatigue- and energy-related signatures, and microbiomics revealed links between gut microbial diversity, recovery, and physiological resilience. Evidence from omics research in soccer supports the potential for individualized approaches to training, nutrition, recovery, and injury prevention. By integrating genomics, proteomics, metabolomics, and microbiomics data, clubs and sports practitioners may design precision strategies tailored to each player’s biological profile. Future research should expand on multi-omics integration, explore gene–environment interactions, and improve representation across sexes, age groups, and competitive levels to advance precision sports medicine in soccer. Full article

Muscle regeneration following injury reveals a striking paradox: the same phenomenon, fiber branching, can serve as both a beneficial adaptation in healthy muscle and a pathological hallmark in disease. In healthy muscle, branched fibers emerge as an adaptive response to extreme mechanical loading, redistributing stress, enhancing hypertrophy, and protecting against injury. Conversely, in conditions such as Duchenne Muscular Dystrophy, excessive and complex branching contributes to mechanical weakness, increased susceptibility to damage, and progressive functional decline. This review explores the dichotomy of fiber branching in muscle physiology, synthesizing current research on its molecular and cellular mechanisms. By understanding the paradoxical nature of fiber branching, we aim to uncover new perspectives for therapeutic strategies that balance its adaptive and pathological roles to improve outcomes for muscle diseases. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM ComplexTea Extract (CTE) and the heat-treated postbiotic (BPL1^® HT) on the cardiometabolic alterations associated with MetS in a murine model. C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and treated with CTE, BPL1^® HT, or their combination for 20 weeks. Metabolic, inflammatory, oxidative, vascular parameters, and fecal microbiota composition were assessed. Both CTE and BPL1^® HT individually attenuated weight gain, organ hypertrophy, insulin resistance, and inflammation. However, their combined administration exerted synergistic effects, fully normalizing body weight, adipocyte size, lipid profiles, HOMA-IR index, and insulin sensitivity to levels comparable to lean controls. Co-treatment also restored PI3K/Akt signaling in liver and muscle, reduced hepatic steatosis, and normalized the expression of inflammatory and oxidative stress markers across multiple tissues. Furthermore, vascular function was significantly improved, with enhanced endothelium-dependent relaxation and reduced vasoconstrictor responses, particularly to angiotensin II. CTE, BPL1^®HT, and the blend prevented bacterial richness reduction caused by HFHS; the blend achieved higher bacterial richness than mice in Chow diet. Additionally, the blend prevented the increase in Flintibacter butyricus, which is associated with MetS clinical parameters, and showed a tendency to increase the abundance of Bifidobacterium. These findings suggest that the combination of CTE and BPL1^® HT offers a potential nutritional strategy to counteract the metabolic and cardiovascular complications of MetS through complementary mechanisms involving improved insulin signaling, reduced inflammation and oxidative stress, enhanced vascular function, and modulation of gut microbiota. Full article

Background: The anabolic window hypothesis suggests a limited post-exercise period for optimal nutrient uptake and utilization. Prior research indicates that miRNAs in extracellular vesicles (EVs) may regulate post-exercise adaptation by influencing protein synthesis. This study aimed to examine the effects of resistance exercise (RE) on physiological parameters and the expression and function of miRNAs transported in EVs. Methods: Twenty resistance-trained male participants (22 ± 2 years) completed a five-week RE program designed for hypertrophy. They consumed maltodextrin and whey protein based on assigned nutrient timing: immediately post-exercise (AE), three hours post-exercise (AE3), or no intake (CTRL). Body composition and knee extensor strength were assessed. Small EVs were isolated and then validated via three methods. Nanoparticle tracking analysis determined EV concentration and size, followed by pooled miRNA profiling and signaling pathway analysis. Results: Skeletal muscle mass significantly increased in AE (p = 0.001, g = 2) and AE3 (p = 0.028, g = 1), and it was higher in AE compared to CTRL (p = 0.013, η² = 0.41), while knee extensor strength improved only in AE (p = 0.032, g = 0.9). Body fat percentage significantly decreased in all groups, AE (p = 0.005, g = 1.5), AE3 (p = 0.024, g = 1), and CTRL (p = 0.005, g = 1.7). Vesicle concentration significantly increased in the AE group (p = 0.043, r = 0.7), while it decreased in the CTRL group (p = 0.046, r = 0.8). Distinct miRNA expression profiles emerged post-intervention: 20 miRNAs were upregulated in AE, while 13 in AE3 and 15 in CTRL were downregulated. Conclusions: Nutrient timing influences training adaptation but is not more critical than total macronutrient intake. Changes in EV-transported miRNAs may regulate anabolic processes via the PI3K-AKT-mTOR and FoxO pathways through PTEN regulation. Full article

Background/Objectives: Numerous studies have documented cardioprotective effects of adiponectin in animal models of cardiometabolic disease (CMD). Adiponectin receptor agonist ALY688 has demonstrated functional significance against pressure overload-induced cardiac remodeling events in a mouse model of heart failure with reduced ejection fraction (HFrEF), potentially through modulation of the systemic metabolome. However, the specific metabolites and their pathophysiological contribution to cardioprotection in cardiac hypertrophy or heart failure remain unclear. This study aimed to characterize systemic metabolic alterations across five tissues in HFrEF and determine how ALY688 modifies these pathways to mediate cardioprotection in the transverse aortic constriction (TAC) model. Methods: Targeted metabolic profiling was performed on heart, liver, muscle, epididymal white adipose tissue (eWAT), and serum collected five weeks post-surgery from wild-type male C57BL/6 mice. Mice underwent either Sham or TAC-induced left ventricular pressure overload, with or without daily subcutaneous ALY688 administration. Metabolites were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and statistically analyzed at the tissue level. Results: Consistent with pathological cardiac remodeling, the comprehensive metabolomic analysis revealed that TAC induced widespread disruption of systemic metabolic homeostasis. ALY688 treatment significantly modified several key metabolite classes, including triglycerides (TGs) and glycosylceramides (HexCer). Notably, ALY688 also altered multiple gut-derived metabolites, including trimethylamine N-oxide (TMAO), 5-aminovaleric acid (5-AVA), and glycodeoxycholic acid (GDCA), highlighting a potential gut–liver–heart axis mediating its cardioprotective effects. Conclusions: These findings demonstrate that ALY688 mitigates TAC-induced metabolic dysregulation across multiple tissues. The identified metabolic signatures suggest that ALY688 exerts cardioprotective effects, at least in part, through restoration of systemic metabolic homeostasis and engagement of a gut–liver–heart metabolic axis. These results provide mechanistic insight into adiponectin receptor agonism and support further exploration of ALY688 as a potential therapeutic strategy for HFrEF. Full article

Background: Resistance training has recently focused more on a high- vs. low-load training approach, suggesting heavier loads optimize strength adaptations through maximal recruitment of motor units, whereas lower loads stimulate a greater hypertrophy response. The purpose of this investigation was to examine and determine significant differences in muscle thickness, strength, and hormonal markers over nine weeks of high- or low-load resistance training. Methods: Seventeen recreationally-trained males were recruited for this study (M_age = 20.4 ± 2.7 years). Participants were split into training with high-loads (85% 1-RM; n = 8) or low-loads (30% 1-RM; n = 9) completing 3 whole-body training sessions per week for 9 weeks. Each session included three working sets per exercise of repetitions to failure. Measures were collected at baseline and every three weeks after of muscle thickness (biceps brachii, triceps brachii, pectoral major, rectus femoris, and biceps femoris) and salivary hormones (basal and acute post-exercise testosterone and cortisol). RM-ANOVAs were conducted to analyze changes in hypertrophy and the hormones, with significance set at p < 0.05. Results: Muscle thickness increased significantly over time for all sites (p < 0.05), with no significant group × time interactions except for the triceps brachii (p = 0.04). There were no significant changes in basal hormone levels or changes from basal to immediately post exercise (p > 0.059). The high-load group showed greater increases in 1-RM following the training program. Conclusions: Our results demonstrate similar hypertrophy regardless of training volume and training load, but greater increases in strength in the high-load group. Hormonal data revealed no significant changes in basal cortisol and testosterone, suggesting similar stress and recovery. While nonsignificant for differences pre-post in either marker, the pattern of a slight decrease in testosterone may be an effect of receptor uptake, and additional monitoring over a longer time interval should be used to track the changes over a full recovery window. Full article

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. Methods: To answer this question, the current study quantified the size and number of slow and fast fibers in biopsies of vastus lateralis skeletal muscle obtained from post-pubertal female baboon offspring 9–12 years old, born to mothers who were untreated (n = 7) or treated during the second half of gestation with letrozole (n = 6; suppressed maternal and fetal estrogen by >90%) or letrozole plus estradiol benzoate (n = 3). Results: Results indicated that skeletal muscle slow and fast fiber growth in female offspring appeared to occur by hypertrophy and that respective size of fibers after the onset of puberty was similar in offspring born to mothers who were untreated or deprived of estrogen in utero. Conclusions: Postnatal myofiber hypertrophy likely reflects the impact of the pubertal surge in and continued exposure of offspring myofibers to ovarian estrogen and is restored to normal in post-pubertal female offspring deprived of estrogen in utero. Full article

Goat meat is widely valued as a healthy option due to its lean nature, yet strategies to further optimize its intrinsic nutritional composition remain a key objective. This study examined the influence of melatonin on muscle development and visceral fat deposition in cashmere goats, focusing on its role in augmenting systemic antioxidant capacity and modifying gut microbiota. Thirty goat kids were randomly assigned to a control or a melatonin-treated (2 mg/kg body weight) group. Melatonin implantation induced a metabolic shift characterized by reduced visceral fat deposition (perirenal, omental, and mesenteric fat; p < 0.05) without impacting intramuscular fat. Concurrently, it promoted muscle accretion, as demonstrated by an increase in crude protein content and hypertrophy of muscle fibers in the Longissimus thoracis et lumborum, Gluteus medius, and Biceps femoris muscles (p < 0.05). These effects were underpinned by an enhanced systemic antioxidant capacity (elevated CAT, GSH-Px, T-AOC, and reduced MDA; p < 0.05), changes in gut microbiota, and a concomitant improvement in gastrointestinal morphology, evidenced by increased rumen papilla length and intestinal villus height. Melatonin enriched beneficial genera (e.g., Succiniclasticum, Butyrivibrio, Akkermansia), which were significantly correlated with reduced adiposity and improved protein deposition. These improvements resulted from the concerted actions of an enhanced systemic antioxidant defense system and a beneficially modulated gut microbial community. This trial observed no effect on intramuscular fat deposition, suggesting that improving intramuscular fat may require a systematic fattening regimen. This study provides a scientific foundation for employing melatonin as a nutritional strategy in goat production to improve meat quality. Full article

Background: Aging elevates reactive oxygen species (ROS) and weakens antioxidant defenses, contributing to cardiac dysfunction. The objective of this study was to determine whether sustained activation of skeletal muscle (SkM) Nrf2 preserves cardiac function during aging and to explore the underlying mechanisms, focusing on myocardial antioxidant pathways. Methods: Tamoxifen-induced SkM-specific Keap1 knockout male mice (iMS-Keap1^flox/flox; SkM-Nrf2 overexpression) were divided into young wild-type (Y-WT), aged wild-type (A-WT), and aged knockout (A-KO) groups. Cardiac performance was evaluated by echocardiography and invasive hemodynamics. Myocardial proteomics identified differentially expressed proteins (DEPs) and enriched biological pathways. Results: Compared with Y-WT, A-WT mice showed impaired left ventricular function, including reduced ejection fraction, prolonged isovolumic relaxation time, blunted inotropic response to dobutamine, and elevated Tau index. These age-related deficits were partially reversed in A-KO mice. Proteomic analysis revealed 561 DEPs between A-WT and Y-WT, and 741 DEPs between A-KO and A-WT, enriched in calcium signaling, Nrf2-mediated oxidative stress response, oxidative phosphorylation, ROS detoxification, and cardiac-specific processes, such as hypertrophy, conduction, and dilated cardiomyopathy. Conclusions: Lifelong SkM-Nrf2 activation strengthens myocardial antioxidant capacity and alleviates age-related cardiac dysfunction. These data support an antioxidant crosstalk between skeletal muscle and the heart, highlighting a potential therapeutic target for aging-associated heart failure. Full article

Background: Long pulse width stimulation (LPWS; 120–150 ms) has the potential to stimulate denervated muscles in persons with spinal cord injury (SCI). We examined whether testosterone treatment (TT) + LPWS would increase skeletal muscle size, leg lean mass and improve overall metabolic health in SCI persons with denervation. We hypothesized that one year of combined TT + LPWS would downregulate gene expression of muscle atrophy and upregulate gene expression of muscle hypertrophy and increase mitochondrial health in SCI persons with lower motor neuron (LMN) injury. Methods: Ten SCI participants with chronic LMN injury were randomized into either 12 months, twice weekly, of TT + LPWS (n = 5) or a TT+ standard neuromuscular electrical stimulation (NMES; n = 5). Measurements were conducted at baseline (week 0), 6 months following training (post-intervention 1), and one week following 12 months of training (post-intervention 2). Measurements included body composition assessment using magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA). Metabolic profile assessment encompassed measurements of resting metabolic rate, carbohydrate and lipid profiles. Finally, muscle biopsy was captured to measure RNA signaling pathways and mitochondrial oxidative phosphorylation. Results: Compliance and adherence were greater in the TT + NMES compared to the TT + LPWS group. There was a 25% increase in the RF muscle CSA following P1 measurement in the TT + LPWS group. There was a recognizable non-significant decrease in intramuscular fat in both groups. There was a trend (p = 0.07) of decrease in trunk fat mass following TT + LPWS, with an interaction (p = 0.037) in android lean mass between groups. There was a trend (p = 0.08) in mean differences in DXA-visceral adipose tissue (VAT) between groups at P1 measurements. For genes targeting muscle atrophy, TT + LPWS showed a trending decline in MURF1 and FOXO3 genes returning to similar levels as TT + NMES before 12 months. Conclusions: These pilot data demonstrated the safety of applying LPWS in persons with SCI. Six months of TT + LPWS demonstrated increases in rectus femoris muscle CSA. The effects on muscle size were modest between groups. Signaling pathway analysis suggested downregulation of genes involved in muscle atrophy pathways. Future clinical trials may consider a home-based approach with more frequent applications of LPWS. Full article

Background/Objectives: A subset of individuals develops persistent symptoms following SARS-CoV-2 infection, including musculoskeletal (MSK) manifestations, a condition known as long COVID (LC). Emerging hypotheses suggest that chronic low-grade inflammation in LC may impair bone metabolism and compromise joint health. However, empirical evidence is limited, and the impact of LC on MSK health, particularly bone and joint integrity, is poorly understood. To determine the influence of LC on MSK function, including bone health, body composition, and joint integrity. Methods: A 12-month longitudinal prospective cohort feasibility study was conducted involving 45 adults with LC and 40 well-recovered (WR) post-COVID-19 controls. Baseline and follow-up assessments included dual-energy X-ray absorptiometry (DXA) for bone mineral density (BMD) and total body composition (TBC), alongside ultrasound of the hand and knee joints to evaluate intra-articular changes. Results: The LC group had more fat in the gynoid, android, and leg regions at each assessment point compared to the controls (p < 0.01). LC showed a significantly lower knee synovial hypertrophy at the baseline, 13.3% compared to WR 45% (p = 0.001), and a marginal improvement in hand synovial hypertrophy, over 12 months, from a median of 2 (IQR 1;5) to 1 (IQR 0;3) (p = 0.012), as observed via MSK ultrasound. No notable differences were found between groups regarding BMD, either in the LC group compared to the control group or overtime. Conclusions: This cohort study of LC adults and controls found no evidence of rapid bone loss; however, adiposity and joint symptoms suggest the need for ongoing monitoring. Future research should focus on MSK markers, muscle function, advanced imaging, and improving MSK health. Full article

Inhaled medications, commonly prescribed for respiratory conditions such as asthma and exercise-induced bronchoconstriction, are increasingly scrutinized in sports medicine due to their potential performance-enhancing effects. Bronchodilators, in particular, may improve lung function, increase oxygen delivery, and influence muscle contractility, potentially enhancing athletic performance. However, supratherapeutic use raises concerns about cardiovascular risks, including tachyarrhythmias and altered autonomic balance, as well as muscle hypertrophy and sprint capacity gains. These effects blur the line between therapeutic use and doping, creating challenges for fair competition. This review explores the mechanisms by which inhaled drugs affect the cardiovascular and muscular systems, summarizes notable doping cases, and evaluates current detection methods. Despite regulatory thresholds established by the World Anti-Doping Agency, assay interpretation remains complicated by inter-individual variability, short drug half-lives, and enantiomeric differences. Addressing these gaps requires refined pharmacokinetic modeling, enantioselective assays, and metabolomic fingerprinting to safeguard both athlete health and the integrity of sport. Full article

Resistance exercise (RE) is a well-known modality to increase skeletal muscle strength and hypertrophy. While both high-load (HL) and low-load (LL) RE stimulate skeletal muscle growth, the effects of RE load on androgen-regulated genes remain unclear. Further, the relationship between circulating and intramuscular androgen-associated targets and muscular strength and mass has not been well defined. Purpose: This investigation therein aimed to examine acute gene and hormone responses to volume- and intensity-equated RE at different loads, examining their relationships with lean body mass (LBM), strength, and circulating and intramuscular androgen-related biomarkers. Methods: Ten resistance-trained males completed one-repetition maximum (1RM) testing, as well as body composition testing, before two volume- and intensity-equated RE sessions, separated by a 7–10 day crossover period. Serum and skeletal muscle samples were collected at baseline, 3 h, and 24 h post-exercise to assess testosterone (TST), dihydrotestosterone (DHT), AR protein, AR mRNA, and AR–DNA binding. Pearson correlations evaluated any potential associations between LBM, strength, and androgen/AR biomarkers. Results: Training load did not significantly impact gene expression, but time effects were observed, whereby MyoD peaked 3 h post-exercise (2.03 ± 1.64 fold; p = 0.005), while AR mRNA decreased at 24 h (0.54 ± 0.42 fold; p = 0.021) versus baseline. LBM also correlated with bench press (r = 0.607, p = 0.048) and leg press (r = 0.705, p = 0.015) 1RM. Serum total TST correlated with leg press 1RM (r = 0.909, p = 0.012), while serum-free TST correlated with AR mRNA fold-change (r = 0.392, p = 0.001) and AR–DNA binding (r = 0.287, p = 0.021). Intramuscular DHT correlated with intramuscular TST (r = 0.415, p < 0.001) and AR protein (r = 0.421, p < 0.001). Lastly, fold changes in AR mRNA were correlated with MyoD mRNA fold changes (r = 0.785, p = 0.007) along with IGF1-Ea mRNA fold changes being significantly correlated with both myogenin mRNA fold changes (r = 0.865, p = 0.001) and AR-DNA binding (r = −0.727, p = 0.017). Conclusions: Despite no observable load-specific effects, RE elicited time-dependent increases in MyoD and AR mRNA expression. This reinforces prior LBM and maximal muscular strength relationship evidence whilst also lending new insights into circulating and intramuscular androgen interactions with AR. Full article

Nutritional supplementation is widely used in resistance training, yet assessment of “hypertrophy” is often confounded by body-composition surrogates. This narrative review, anchored in mechanistic plausibility, integrates trials reporting morphology-direct outcomes (ultrasound/MRI). Across 46 eligible trials, protein/essential amino acids (EAA) showed consistent benefits when daily intake was <1.6 g·kg⁻¹·day⁻¹ or when per-meal leucine provision was <2–3 g; effects plateaued once intakes exceeded ~2.0 g·kg⁻¹·day⁻¹. Creatine monohydrate (3–5 g·day⁻¹, with or without loading) produced measurable increases in muscle thickness or cross-sectional area in interventions lasting ≥8–12 weeks, mediated by enhanced training volume and quality. β-hydroxy-β-methylbutyrate (HMB, 3 g·day⁻¹) demonstrated conditional utility during high training stress or caloric deficit, but was largely neutral in well-fed, resistance-trained cohorts. Adjuncts such as omega-3 fatty acids (1–2 g·day⁻¹), citrulline (6–8 g pre-exercise), and collagen (10–15 g·day⁻¹ plus vitamin C) primarily facilitated training tolerance, recovery, or connective-tissue adaptation, rather than driving hypertrophy directly. A tiered model is proposed: protein/EAA as the foundation, creatine as amplifier, HMB as conditional agent, and adjuncts as facilitators. Methodological heterogeneity, short intervention length, and inconsistent imaging protocols remain limiting factors, underscoring the need for standardized ultrasound/MRI and adequately powered, preregistered trials. Full article

Generalized lipodystrophies (GLs) are rare diseases characterized by a lack of body fat. When patients with a GL phenotype are referred with a presumptive diagnosis of congenital generalized lipodystrophy (CGL) but genetic testing for known pathogenic variants is negative, the diagnosis of acquired generalized lipodystrophy (AGL) becomes a more likely diagnosis. No single test confirms such a diagnosis, and it is crucial to recognize the similarities and differences between these diseases. We review the literature and report four GL cases from our lipodystrophy outpatient clinic, highlighting the main points for an accurate diagnosis. Similarities: phlebomegaly, umbilical scar protrusion, loss of Bichat’s fat pad, muscle hypertrophy, and hepatomegaly can occur in both. Cirrhosis can also arise, but in AGL, it occurs as a consequence of hepatic steatosis and also due to autoimmune hepatitis. Insulin resistance is frequent, and patients present acanthosis nigricans and acrochordons and may develop difficult-to-control diabetes and its complications, despite very high daily doses of insulin. Low HDL and hypertriglyceridemia are frequent and may progress to acute pancreatitis. Serum leptin levels are typically low and contribute to hyperphagia. Differences: AGL patients’ body fat loss occurs gradually in childhood or adolescence, whereas CGL patients are born with the characteristic phenotype. Evaluating photographs of AGL patients in the first years of life can provide evidence of this selective and gradual fat loss. Some AGL patients may have panniculitis (inflamed and painful subcutaneous nodules), with or without autoimmune diseases. In conclusion, recognizing both similarities and differences is crucial for making an accurate diagnosis and ensuring the most appropriate treatment. Full article