Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(3), P. 454 - 499

Published: Jan. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Language: Английский

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Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

Journal of Cachexia Sarcopenia and Muscle, Journal Year: 2024, Volume and Issue: 15(3), P. 1121 - 1133

Published: March 31, 2024

Abstract Background Cytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging sarcopenia due to their roles inflammaging. In this study, we aim explore association of cytokines with aging traits further identify significant inflammation factors. Methods Bidirectional Mendelian randomization (MR) analysis was used causality. Forty‐one kinds circulation were set exposures, data from summary genome‐wide study (GWAS) containing three cohorts 8293 healthy participants European ancestry 1983 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate‐to‐vigorous physical activity (MVPA) levels, able walk or cycle unaided for 10 min (AWCU10) telomere length selected outcomes. Data outcomes obtained meta‐GWAS UK Biobank, sample sizes ranged 69 537 472 174. Low hand strength defined by Working Group on Sarcopenia Older People (EWGSOP) Foundation National Institutes Health (FNIH) cut‐off points, respectively. Other outcome measured according Biobank raw cohorts' criteria. We two significance thresholds single nucleotide polymorphisms (SNPs) associated exposures obtain adequate SNPs (5 × −6 5 −8 ). Inverse‐variance weighted, MR‐Egger weighted median employed estimate Results Twenty‐seven identified relate causally, most only one trait. IL16 (interleukin‐16), CTACK (cutaneous T‐cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) PDGFbb (platelet‐derived factor BB) proven causally at least trait both analyses thresholds. (0.977 [0.956–0.998] EWGSOP 0.933 [0.874–0.996] FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995–1.000]) AWCU10 (1.008 [1.003–1.013]). (1.013 [1.007–1.019] 1.090 [1.041–1.142] (0.990 [0.986–0.994]) (0.998 [0.983–0.994]). The results indicated that has effect (1.032 [1.001–1.063] EWGSOP), (0.994 [0.988–1.000] 0.993 [0.988–0.998]) (1.006 [1.000–1.012]). (1.016 [1.001–1.030]) (1.011 [1.007–1.015]). Reserve MR also proved unidirectional effects. Conclusions related traits, effects IL16, CTACK,

Language: Английский

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Research Progress on the Effect and Mechanism of Exercise Intervention on Sarcopenia Obesity

Clinical Interventions in Aging, Journal Year: 2024, Volume and Issue: Volume 19, P. 1407 - 1422

Published: Aug. 1, 2024

With the increasingly severe situation of obesity and population aging, there is growing concern about sarcopenia (SO). SO refers to coexistence sarcopenia, which imposes a heavier burden on individuals society compared or alone. Therefore, comprehending pathogenesis implementing effective clinical interventions are vital for its prevention treatment. This review uses comprehensive literature search analysis PubMed, Web Science, CNKI databases, with terms including "Sarcopenic obesity", "exercise", "cytokines", "inflammation", "mitochondrial quality control", "microRNA", covering relevant studies published up July 2024. The results indicate that complex, involving mechanisms like age-related changes in body composition, hormonal alterations, inflammation, mitochondrial dysfunction, genetic epigenetic factors. Regarding exercise SO, aerobic can reduce fat mass, resistance increase skeletal muscle mass strength, combined achieve both, making it optimal intervention SO. potential by may prevent treat include regulating cytokine secretion, inhibiting inflammatory pathways, improving quality, mediating microRNA expression. emphasizes effectiveness mitigating sarcopenic through multifactorial mechanistic insights into exercise's therapeutic effects. Understanding these informs targeted strategies aimed at alleviating societal individual burdens associated

Language: Английский

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TLR/NLRP3 Inflammasome signaling pathways as a main target in frailty, cachexia and sarcopenia

Tissue and Cell, Journal Year: 2025, Volume and Issue: 93, P. 102723 - 102723

Published: Jan. 9, 2025

Language: Английский

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Identification of association between mitochondrial dysfunction and sarcopenia using summary-data-based Mendelian randomization and colocalization analyses

The Journals of Gerontology Series A, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Mitochondrial dysfunction has been demonstrated to be an important hallmark of sarcopenia, yet its specific mechanism remains obscure. In this study, mitochondrial-related genes were used as instrumental variables proxy for mitochondrial dysfunction, and summary data sarcopenia-related traits outcomes examine their genetic association. A total 1,136 from the human MitoCarta3.0 database extracted. Genetic instruments them obtained gene expression quantitative trait locus (eQTLs) study (n = 31,684). Aggregated [(including low hand grip strength (LHGS), appendiceal lean mass (ALM), usual walking pace (UWP) provided by large-scale genome-wide association studies (GWASs). We integrated eQTLs with GWAS estimate between sarcopenia using summary-data-based Mendelian randomization (SMR) analysis. Additionally, we implemented colocalization analysis strengthen Finally, skeletomuscular tissue 706) was validate primary findings. By integrating results three traits, two genetically associated identified, namely UQCC1 (tier 2 evidence) ETFDH 3 evidence). Specifically, elevated levels increased LHGS risk (OR 1.114; 95% CI, 1.078-1.152; P-FDR 1.70 × 10-7), which matched negative it UWP (Beta -0.015; -0.021 - -0.010; 6.70 10-5). Furthermore, found both lower ALM 0.031; 0.020-0.042; 1.41 10-6) 0.013; 0.006-0.021; 0.029). Of note, consistent replicated in tissues, further suggesting our findings robust. Our analyses revealed genes, i.e., ETFDH, highlighting pivotal role driven these pathogenesis sarcopenia. Importantly, candidate represent potential clinical drug targets treatment

Language: Английский

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Cut-off values for the muscle mass indices determined using DXA in healthy Polish adults – a comparison to EWGSOP2 recommendation

Aging, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Background: Muscle mass measurements are vital for predicting health outcomes and diagnosing muscle disorders. This study provides reference data appendicular lean (ALM) total (TLM) in healthy Polish adults with normal strength physical performance as per EWGSOP2 guidelines. Methods: The included volunteers functional status. Lean was measured using Hologic Horizon DXA. Mean values of TLM, ALM, fat-free (FFM), indices (TLMI, ALMI, FFMI) were calculated seven age groups (by decade). Cut-off points equivalent to T-scores -1 -2 standard deviations (SDs) below the young adult mean (ages 20-39) determined. Results: Data from 1,111 participants (328 men, 46.3 ± 20 years; 783 women, 43.7 23 years) analyzed. In adults, ALM 28.1 kg (men) 17.2 (women), ALMI 8.6 kg/m² 6.1 (women). Low cut-off (2 SDs below) 18 10.9 6 4.3 (ALMI) men respectively. Men exhibited significantly greater than women across all (P < 0.001). declined both genders, following a nonlinear pattern, except men. Conclusions: first population-based TLM aged 20-89 years, integrating criteria performance.

Language: Английский

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THE IMPACT OF SARCOPENIA ON POSTOPERATIVE OUTCOMES IN ESOPHAGEAL CANCER PATIENTS UNDERGOING ESOPHAGECTOMY: A SYSTEMATIC REVIEW AND META-ANALYSIS

Clinical and Preventive Medicine, Journal Year: 2025, Volume and Issue: 1, P. 162 - 170

Published: Jan. 20, 2025

Introduction. Esophageal cancer remains a major global health challenge, ranking among the leading causes of cancer-related mortality. Esophagectomy, standard treatment for resectable cases, is associated with high rates postoperative complications, significantly impacting patient outcomes. Among various risk factors, sarcopenia—a condition characterized by decreased skeletal muscle mass and strength—has emerged as potential predictor adverse However, its precise influence on esophagectomy-related morbidity mortality unclear, warranting further investigation. Aim. This systematic review meta-analysis aimed to evaluate impact sarcopenia early outcomes in patients undergoing esophagectomy esophageal cancer. Specifically, we assessed association between anastomotic leakage, Materials methods. A literature search was conducted MedLine Cochrane Library Central studies published January 2020 September 2024, adhering PRISMA guidelines. Eligible included cohort clinical trials comparing sarcopenic non-sarcopenic esophagectomy. Data extraction focused demographics, assessment methods, performed using random-effects model, results expressed log odds ratios 95% confidence intervals (CIs). Heterogeneity I² statistic, publication bias evaluated through funnel plot asymmetry tests. Results. total 10 studies, encompassing 1,382 patients, met inclusion criteria. The pooled analysis revealed that an increased complications (log ratio: 0.725, CI: 0.221 1.229; p = 0.005), moderate heterogeneity (I² 49.3%). no significant found leakage -0.376, -1.537 0.785; 0.525), despite 74.1%). Similarly, relationship observed 0.803, -2.200 3.806; 0.600), 63.1%). Conclusions. Sarcopenia increases esophagectomy, underscoring need preoperative targeted nutritional or rehabilitation interventions. inconclusive. Further research standardized definitions larger cohorts necessary refine stratification optimize perioperative care strategies.

Language: Английский

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Assessing causality between inflammatory bowel diseases with frailty index and sarcopenia: a bidirectional Mendelian randomization study

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Jan. 5, 2024

Abstract Background Previous studies have found that frailty and sarcopenia are commonly diagnosed in inflammatory bowel disease (IBD) patients, indicating an association between these conditions. Nonetheless, the cause‒effect connection IBD, frailty, remains unclear. Methods We sourced genetic variants for exposures outcomes from publicly accessible, extensive genome-wide (GWAS). Specifically, we obtained IBD data International Genetics Consortium, index (FI) United Kingdom Biobank Swedish TwinGene, a recent GWAS meta-analysis. Five methods, including inverse variance weighted (IVW), simple mode, MR-Egger, median, were used to proceed with MR estimates. also performed heterogeneity horizontal pleiotropy tests. Results Our results indicated positive causal relationship ulcerative colitis (UC) (IVW: β = 0.014, 95% CI, 0.006 0.021, p 0.001) Crohn's (CD) 0.012; 0.018, 2e−04) FI. However, uncovered no proof of cause-and-effect UC 0.001, −0.015 0.017, 0.344) or CD 0.003, −0.009 0.015, 0.214) sarcopenia. Additionally, order, discovered FI on this study. Conclusion The analysis showed FI, patients may exhibit aging-related characteristics. Therefore, assessments should be conducted as early possible patients.

Language: Английский

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Related factors of sarcopenia risk in Chinese older people - a cross-sectional study

Psychology Health & Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 15

Published: Jan. 17, 2025

Numerous factors, including age chronic disease, level of education, and depression, affect the health function skeletal muscles. However, it is still unclear which factors muscle in older groups across range segments. Decision tree logistic regression models were employed this study to examine that influence adults' likelihood developing sarcopenia. The database information China Health Retirement Longitudinal Study (CHARLS) 2015 was selected, a sample 2965 people who met inclusion criteria screened. Logistic research revealed while height (p = 0.001, OR:0.979, 95%CI:0.967–0.992), triglycerides 0.036, OR:0.999,95%CI:0.998–1.000), education 0.004, OR:0.684,95%CI:0.530–0.883), endowment insurance 0.003, OR:0.598,95%CI: 0.427–0.839) protective variables against sarcopenia adults, < OR:1.094,95%CI:1.079–1.110), depression OR:1.283,95%CI:1.089–1.512), disease(p 0.012, OR:1.266,95%CI: 1.054–1.522) risk for condition. According decision model, biggest determinant an person's chance age, followed by social communication, insurance. In aging Chinese population, positively correlated with adversely height, triglycerides, Level primary factor determining adults aged 60–69, influencing 70–79. To prevent intervene earlier beginning progression elderly, advised knowledge condition be raised among population.

Language: Английский

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The Dietary Inflammatory Index and Sarcopenia in Older Adults in Four Chinese Provinces: A Cross-Sectional Study

Nutrients, Journal Year: 2025, Volume and Issue: 17(3), P. 478 - 478

Published: Jan. 28, 2025

Background: Sarcopenia associated with aging severely affects the quality of life elderly; diets have been shown to elicit an inflammatory response in body, and that promote inflammation may lead damage muscles. The Dietary Inflammatory Index (DII) has developed quantify potential individual diets. Therefore, this study aimed investigate association between DII, sarcopenia its components elderly Chinese people. Methods: In study, data were obtained from China Nutrition Improvement Strategies Applications for Elderly Research Programme. An assessment was carried out according Asian Working Group on Sarcopenia’s (AWGS2019) criteria. DII calculated using food intake FFQ method, then quartile method used categorize subjects into four groups. Multifactor logistic regression conducted examine associations components. Results: This included 993 over age 65, prevalence 20.2%. mean score population 0.99 ± 0.1. After adjusting confounders age, gender, marital status, educational level, risk 1.66 times higher group Q4 than Q1 (p-trend < 0.05). However, relationship is not statistically significant when other more confounding factors are added. Nevertheless, further analyzing components, it found after model, a muscle strength loss (OR = 1.65, p-trend Conclusions: Higher scores increase older adults. By guiding adults adopt anti-inflammatory diet, health can be improved terms increased strength. Further cohort or interventional studies necessary validate our findings.

Language: Английский

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