Young-onset diabetes in South Asians frequently manifests in lean individuals, but the metabolic drivers of this phenotype remain poorlycharacterised. This study aimed to evaluate the clinical, biochemical, and insulin-related indices of lean, non-autoimmune young-onset diabetes mellitus (DM) among Bangladeshi young adults. This comparative cross-sectional study (2023-2024) enrolled 373 participants (aged 18-34 years) categorised into four groups based on glycemic status and body mass index (BMI): Lean DM (n = 53), obese DM (n = 125), lean non-DM (n = 78), and obese non-DM (n = 117) from the Young-diabetes Clinic of the Department of Endocrinology, Bangladesh Medical University, Dhaka after excluding those with positive islet autoantibodies, low C-peptide, pancreatic pathology, and monogenic variants. β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR) were quantified using the HOMA2 C-peptide calculator. Lean DM participants were comparable to other groups in age, sex, and family history, though smoking was more prevalent than in lean controls (p < 0.05). Prevalence of central obesity and blood pressure levels of lean DM were similar to those of lean controls, but the lipid profile was comparable to that of obese DM. The median HbA1c was higher in lean DM than in obese DM (11.6% vs. 8.5%; p < 0.001), while their median HOMA2-B was the lowest across all other groups (p < 0.01). The HOMA2 - IR in lean DM was lower than in obese DM but significantly higher than in lean controls and mirrored the resistance seen in the obese non-DM group (p < 0.001). Lean young-onset diabetes in Bangladesh appears to be a phenotype of disproportionate insulin secretory defect with only modest insulin resistance and metabolic dysfunction. These features highlight the need for targeted screening and individualised management.
Metabolic Dysfunction Associated Steatotic Liver Disease with Increased Alcohol Intake (MetALD) is a distinct clinical entity characterized by hepatic steatosis driven by both metabolic syndrome and alcohol use. This study aimed to characterize the clinical presentation and evaluate major liver outcomes (MALO) and all-cause mortality in patients with lean versus non-lean MetALD. We conducted a retrospective cohort study using data from the Veterans Analysis of Liver Disease (VALID) cohort. Lean MetALD was defined as MetALD in individuals with a body mass index <25 kg/m2 (<23 kg/m2 in Asians). We used a multivariable Fine and Gray competing risk model to assess the association between lean MetALD and MALO and all-cause mortality. A total of 98,076 veterans with MetALD were included, of whom 12,613 met criteria for lean MetALD, between 1/1/2011 and 12/31/2022, with follow-up through 5/31/2023. Patients with lean MetALD had a higher AUDIT-C, and AST:ALT ratio (AST>ALT; 42.9 vs. 37.9 IU/mL), while non-lean MetALD patients had more cardiometabolic risk factors and AST<ALT (38.1 vs. 49.3 IU/mL). Lean MetALD was independently associated with a 28% higher risk of MALO (aHR 1.28, 1.18-1.38) and a 82% higher risk of all-cause mortality (aHR 1.82, 1.74-1.91) compared with non-lean MetALD. Patients with lean MetALD displayed clinical features more consistent with alcohol-associated liver disease, while non-lean MetALD patients were clinically more similar to MASLD. Lean MetALD is associated with significantly increased risks of liver-related complications and mortality, reinforcing the need for tailored management strategies targeting alcohol use disorder for this high-risk subgroup.
This review article provides a comprehensive overview of lean authoring in the pharmaceutical industry based on the experience of medical writing leaders, emphasizing its importance for efficiently creating clinical study reports (CSRs) and other clinical documents. Lean authoring is defined as an approach focused on delivering unambiguous, clear, concise, and objective content that meets regulatory reviewer expectations. This will better ensure accessibility, eliminating unnecessary details, and tailoring content to meet the following needs of regulatory reviewers during what is essentially a non-linear review process: a) fast navigation to decision-critical information, b) a clear, logical trail from study design to analyses to results, c) low cognitive burden, and d) fewer review questions resulting from ambiguous language and inconsistency. The benefits of lean authoring include improved readability and reusability of content, enhanced efficiency and cost-effectiveness in document preparation, and more efficient regulatory reviews. These benefits have been observed across many industries. And yet, challenges in implementing lean authoring methods, including resistance to change, are common. To help companies counter resistance to change, this article outlines the benefits of lean authoring and a step-by-step approach to adopting lean authoring methods, understanding regulatory reviewers' needs, and developing a robust change management plan. Healthcare agency regulatory reviewers have stated their preference for clear and concise information. Our goal is to influence the pharmaceutical industry to adopt lean authoring to achieve this. By optimizing the authoring process, we aim to increase the efficiency of the process, improve the quality of CSRs, and reduce the burden of regulatory reviews.
To analyze the research status, hotspots, and frontiers of lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) in the past 20 years using bibliometrics, providing references for further related research. Literature on lean MASLD was retrieved from the Web of Science Core Collection database. Visual analyses of publication trends, author distribution, research institutions, journal distribution, cited documents, and keywords, were performed using VOSviewer, the "Bibliographic" package in R, and CiteSpace software. A total of 2008 documents were included. The publication output on lean MASLD increased annually and peaked in 2023. This literature originated from 82 countries/regions, with the United States contributing the most publications. Harvard University was the institution with the highest publication count, PLOS ONE was the top journal in this field, and Prof Wong, Vincent Wai-Sun from The Chinese University of Hong Kong was the most productive author. The research on lean MASLD at that time primarily focused on etiology and treatment (e.g., hepatic steatosis, insulin resistance, metabolic syndrome, oxidative stress, inflammation, abdominal obesity, sarcopenia, patatin-like phospholipase domain-containing 3 gene, and gut microbiota), as well as epidemiology and diagnostic methods. This study systematically depicted the 2-decade developmental trajectory of lean MASLD using bibliometric methods for the first time, and provides academic references for clinicians and scholars to grasp the field's hotspots, frontiers, and evolutionary trends.
Loss of lean mass in proportion to total weight loss is observed with incretin mimetic therapies such as tirzepatide and has the potential to adversely affect health and function. Apitegromab is an investigational, fully human monoclonal antibody that selectively inhibits myostatin activation and is, thereby, capable of increasing muscle mass. In the randomized, double-blind, placebo-controlled phase 2 EMBRAZE study, adults with overweight or obesity (n = 102) were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg kg-1) or tirzepatide plus placebo. At week 24, apitegromab resulted in a least square mean (80% confidence interval (CI)) of 1.9 (1.2-2.7) kg less lean mass loss than placebo (P = 0.001), despite similar total body weight loss between groups, representing a 54.9% retention of lean mass relative to placebo. In participants receiving apitegromab, trough concentrations of apitegromab and total latent myostatin, a pharmacodynamic marker, both increased over time and reached a plateau after approximately 16 weeks. Incidence of adverse events (AEs) (% (95% CI)) was generally similar across apitegromab-treated participants and placebo-treated participants, with 39 of 51 (76% (63-86%)) and 36 of 51 (71% (57-81%)) participants experiencing an AE, respectively. Serious adverse events (SAEs) were balanced and experienced by one of 51 (2% (0-10%)) participants in each arm. In summary, this proof-of-concept study demonstrated that selective targeting of myostatin by apitegromab was well tolerated and effective in preserving lean mass when combined with tirzepatide. ClinicalTrials.gov identifier: NCT06445075 .
Cervical cancer is the most common malignancy among South African (SA) women of reproductive age, with women living with HIV (WLWH) facing a six-fold higher susceptibility. The National Department of Health recommends baseline cervical cancer screening (CCS) for WLWH upon HIV diagnosis. SA's reported CCS rate is 19.3%, despite the World Health Organization (WHO)'s recommended 2030 target of 70%. AIDS Healthcare Foundation initiated the CerviScreen programme to improve CCS rates using Lean thinking. To evaluate the effect of the programme on CCS coverage over a 7-month period at selected sites in the Eastern Cape and KwaZulu-Natal provinces of SA. This quantitative, controlled before-and-after study retrospectively evaluated changes in CCS coverage at purposively selected quality improvement programme (QIP) sites, compared with matched control sites. Key CCS indicator data from Lean A3 tools were analysed. Repeated analysis of variance measures tested changes in CCS proportions over time, at a p<0.05 significance level. Nine CerviScreen and nine control sites per province were assessed. Significant increases in CCS mean proportions were observed at QIP sites in KwaZulu-Natal (5% - 62.9%; F=8.336, p<0.001) and Eastern Cape (21.2% - 82.4%; F=15.525, p<0.001) provinces. Differences in the change of mean proportions between CerviScreen and control sites were not statistically significant in KwaZulu-Natal (F=0.022, p=0.884) and Eastern Cape (F=0.882, p=0.362). Clinically significant improvements were observed, with the estimated marginal mean at KwaZulu-Natal QIP sites consistently surpassing control sites from month 3 onwards. Eastern Cape sites maintained over 80% coverage from month 4. Screening coverage trends differed significantly between provinces (F=11.12, p=0.004). Lean thinking, through the CerviScreen programme, has potential to enhance and accelerate CCS among SA WLWH toward attaining the WHO target. The findings underscore the importance of adopting systematic quality improvement approaches, highlighting the need for scale-up of Lean thinking in primary healthcare settings to address underperforming indicators.
Lean management (LM) has been implemented in healthcare organisations, promising efficient operations, rapid patient access to care, improved staff satisfaction and lower costs. However, use of LM is questioned because there is no strong evidence of its outcomes, so proof of long-term and organisation-wide use is needed. The aim of the study is to increase understanding of the long-term effects of LM in healthcare. This is a case study done at the Helsinki University Hospital in Finland. A retrospective qualitative study was conducted in three sectors (A, B and C) of the hospital. Fourteen healthcare leaders from three sectors participated in interviews by answering structured and open-ended questions. The interviews were used to evaluate the outcomes that are experienced by the leaders in the hospital setting over a five-year period and evaluate indicators that they used to assess these outcomes. The interviews were analysed using qualitative and quantitative content analysis with ATLAS.ti analysis software (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). The outcomes of LM can be grouped into three main categories (organisation, patient and staff) that are divided into six subcategories: experiential, care-related, work-related, economic, leadership and management, and image effects. The leaders experienced the greatest benefits on the organisation level, as it enhanced the effectiveness of the organisation's structure and operations, fostered continuous development, improved staff retention and attraction and promoted patient-centredness. According to the leaders, the most important benefits for patients included improved access to care, better care flow, enhanced safety of care and greater participation in improving operations. In addition, the leaders highlighted that the biggest benefits for staff, were increased work satisfaction, work competence, work commitment and ethical behaviour. We found that the use of LM also has disruptive and contradictory effects caused by the lack of organisation-wide Lean commitment and structure, and the media have bias towards negative portrayals of hospital efficiency. We found that six subcategories provide a comprehensive framework for qualitatively assessing organisation-wide experienced outcomes of LM in the hospital. Our findings emphasise that the organisation should be fully committed to the Lean method, and its structure should be clear so that the best benefits of LM can be achieved. We noticed that more qualitative LM research is needed to complement the Lean knowledge gained from quantitative research, develop more comprehensive and high-quality evaluation indicators and increase evidence for its use in healthcare.
Endometrial cancer is the second most common gynaecologic cancer in women worldwide. Due to the biology of endometrial cancer, most patients are overweight. Standard uptake value (SUV) measurements are known to vary depending on the patient's body weight. We aimed to evaluate whether lean body mass-adjusted 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters [lean body mass-corrected standardized uptake value (SUL)-based metrics] are superior to conventional SUV-based parameters for predicting adverse histopathologic features in overweight patients with endometrial cancer, and to explore their association with progression-free survival (PFS). In this retrospective single-center study, 73 overweight patients with endometrial cancer who underwent preoperative 18F-FDG PET/CT followed by primary surgery were included. SUV- and SUL-based metabolic parameters were compared with histopathologic risk factors. ROC analyses were performed to determine discriminatory performance and optimal cut-off values. PFS was assessed using Kaplan-Meier analysis. SUVmean (SULmean) demonstrated significant associations with deep myometrial invasion, lymphovascular space invasion, lymph node involvement, and higher tumor grade. In ROC analysis, SULmean showed moderate discriminatory ability for lymph node involvement (area under the curve: 0.78). However, PFS did not differ significantly between groups stratified by the ROC-derived SULmean cut-off (log-rank p=0.46). Lean body mass-adjusted PET parameters, particularly SULmean, were more strongly associated with adverse histopathologic features than conventional SUV metrics in overweight patients with endometrial cancer. Although SUL-based parameters may contribute to preoperative risk assessment, their prognostic value for survival remains uncertain. Endometriyal kanser, dünyada kadınlar arasında en yaygın ikinci jinekolojik kanserdir. Endometriyal kanserin biyolojisi nedeniyle, çoğu hasta aşırı kiloludur. Standart alım değeri (SUV) ölçümlerinin, hastanın vücut ağırlığına bağlı olarak değişebileceği bilinmektedir. Bu çalışmanın amacı, aşırı kilolu endometriyal kanserli hastalarda vücut yağsız kütlesine göre ayarlanmış 18F-fluorodeoksiglukoz pozitron emisyon tomografi/bilgisayarlı tomografi (18F-FDG PET/CT) parametrelerinin [yağsız vücut kütlesine göre düzeltme yapılmış standartlaştırılmış alım değeri (SUL) tabanlı ölçütler] konvansiyonel SUV tabanlı parametrelerden daha üstün olup olmadığını araştırmak ve bu parametrelerin progresyon-free survival (PFS) ile ilişkisini incelemektir. Bu retrospektif tek merkezli çalışmada, preoperatif 18F-FDG PET/CT çekimi yapılan ve ardından primer cerrahi uygulanan 73 aşırı kilolu endometriyal kanser hastası dahil edilmiştir. SUV- ve SUL tabanlı metabolik parametreler, histopatolojik risk faktörleriyle karşılaştırılmıştır. ROC analizleri, ayırıcı performansı ve optimal kesme değerlerini belirlemek için yapılmıştır. PFS, Kaplan-Meier analizi ile değerlendirilmiştir. SULmean (SULmean), derin miyometrial invazyon, lenfovasküler alan invazyonu, lenf nodu tutulumu ve yüksek tümör derecesi ile anlamlı ilişkiler göstermiştir. ROC analizinde, SULmean, lenf nodu tutulumu için orta derecede ayırt edici bir yetenek göstermiştir (eğri altında alan: 0.78). Ancak, ROC tabanlı SULmean kesme değeri ile gruplar arasındaki PFS, anlamlı şekilde farklılık göstermemiştir (log-rank p=0.46). Yağsız vücut kütlesine göre ayarlanmış PET parametreleri, özellikle SULmean, aşırı kilolu endometriyal kanserli hastalarda konvansiyonel SUV ölçütlerinden daha güçlü bir şekilde olumsuz histopatolojik özelliklerle ilişkilidir. SUL tabanlı parametreler, preoperatif risk değerlendirmesine katkı sağlasa da, hayatta kalma üzerindeki prognostik değerleri belirsizdir.
Enhancing operating room efficiency while preserving resident surgical education remains a priority for teaching hospitals. Applying Lean principles to pair residents' step-level risk and comfort perceptions with step-level time may reveal training targets that reduce operative duration and improve safety. This study quantified the relationship between residents' step-level perceived risk or comfort and operative time during filum terminale lysis (FTL) and primary vagus nerve stimulator (VNS) placement. Attending pediatric neurosurgeons defined 11 FTL and 10 VNS placement steps. A 2-part survey captured step-specific comfort and perceived risk from junior residents, senior residents, and faculty members (for VNS placement, 11 junior residents, 10 senior residents, and 3 faculty members were surveyed; for FTL, 11 junior residents, 9 senior residents, and 4 faculty members). Responses were mapped to a risk matrix with a "danger zone" (high-risk score of 3-5 and low-comfort score of 1-3) and a "safe zone" (low-risk score of 1-2 and high-comfort score of 4-5). Step-level times were prospectively recorded across FTL (n = 16) and VNS (n = 24) cases. Analyses included the Fisher's exact test, Spearman correlations, and linear-by-linear tests for training-level trends. Risk-matrix analysis showed significant junior resident-faculty member differences for both procedures, with no senior resident-faculty member differences. In FTL, significant junior resident-faculty member differences were observed for dural closure (p = 0.004). In VNS placement, junior residents more often labeled carotid sheath exposure, vagus nerve exposure, and lead placement as the danger zone (all p = 0.0027). Excluding closure, VNS placement demonstrated positive associations between perceived danger and both step time and share of cases (for junior residents, ρ = 0.73, p = 0.025; senior residents, ρ = 0.75, p = 0.020; faculty members, ρ = 0.58, p = 0.10). In FTL, no association was observed. Training-level trends showed increasing high comfort (≥ 4) with seniority across most steps (10/11 steps for FTL; 7/10 steps for VNS placement). Step timing highlighted skin closure for VNS placement (median [IQR] 1769 [1447-2304] seconds) and dorsal bony exposure (700 [427-1037] seconds), dural closure (932 [336-1387] seconds), and fascial closure (695 [563-828] seconds) for FTL as the most time-consuming phases. Combining step-level risk-comfort matrices with timing can yield procedure-specific teaching targets. In FTL, danger perception aligns with time burden, supporting focused coaching on dural closure and exposure; in VNS placement, the main time-intensive step is low-risk closure, which may yield areas for improvement via workflow and team-based interventions, while danger-labeled exposure/lead steps merit targeted supervision for safety. This Lean principle-based framework enables training level-specific interventions to improve both efficiency and safety.
[This corrects the article DOI: 10.3389/fnut.2026.1800546.].
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Retrospective cross-sectional study. To investigate the relationship between sarcopenia-related markers and artificial intelligence (AI)-derived three-dimensional (3D) volumetric indices of lumbar muscles. Sarcopenia is characterized by loss of skeletal muscle mass and physical function. Although appendicular skeletal muscle mass (ASM) is widely used for sarcopenia assessment, reliable evaluation of lumbar paraspinal muscles remains limited. AIbased 3D volumetric analysis may provide a reproducible approach for muscle assessment. This single-center retrospective cross-sectional study included 58 women aged ≥65 years who underwent lumbar computed tomography and sarcopenia assessment. AI-derived 3D volumetric analysis was performed using TotalSegmentator implemented in 3D Slicer. Volumetric indices were calculated as muscle volume (cm3) divided by height3 (m3). Associations between volumetric indices and ASM measured by dual-energy X-ray absorptiometry were evaluated using Pearson correlation and multivariable linear regression analyses. Among the 58 participants, 25 were classified as having sarcopenia. Appendicular skeletal muscle mass index (ASMI) was not significantly associated with paraspinal muscle volume indices. In contrast, the iliopsoas muscle volume index showed a significant positive correlation with ASMI (r=0.424, p<0.001). No significant differences in AI-derived 3D lumbar muscle volumetric indices were observed between sarcopenic and non-sarcopenic groups. Paraspinal muscle volume indices were not significantly associated with ASMI, whereas iliopsoas muscle volume indices showed a significant association. These findings suggest that the iliopsoas muscle may better reflect systemic skeletal muscle mass than paraspinal muscles in older women.
Evidence on the association between dynamic changes of obesity throughout the life course and chronic kidney disease (CKD) remains lacking. This study aimed to investigate the relationship between body shape trajectories from early to middle age and CKD, supplemented by Mendelian randomization to explore potential causal relationships. Body shape at different ages in Henan Rural Cohort Study was retrospectively assessed by Stunkard body diagram, and group-based trajectory models were employed to identify trajectories of body shape. Logistic regression model was employed to assess the relationships between body shape trajectories and eGFR decrease, albuminuria, and CKD. Life expectancy and CKD-free life expectancy (CFLE) were calculated by the Sullivan method. Two-sample MR analysis was used to explore potential causal relationship. Five body shape trajectories from the 17,496 subjects were identified: lean-stable, lean-marked increase, medium-stable, medium-moderate increase, and heavy-stable. Compared to the lean-stable group, the adjusted odds ratios (OR) with 95% CI for CKD in the heavy-stable group were 1.37 (1.01, 1.86) in men, and 1.28 (1.02, 1.61) in women, respectively. Additionally, CFLE was shortest in the heavy-stable group for both genders. Corresponding genetic, the causal risk effects of CKD were 1.18 (1.01, 1.37) and 1.36 (1.15, 1.62) for childhood BMI and adult BMI, respectively. Participants with stable heavy body shape throughout the life course had the highest prevalence of CKD and the shortest CFLE, and genetic evidence supported causality for the associations. This study identifies a lifelong heavy body shape as a risk marker for chronic kidney disease.
Exercise training has been associated with metabolic improvements in bariatric patients beyond weight and fat loss, potentially involving modulation of the gut microbiota. We investigated whether exercise-related microbial changes are associated with metabolic adaptations in women undergoing Roux-en-Y gastric bypass (RYGB) by combining a randomized controlled exercise intervention trial in women post-surgery with a human-to-mouse fecal microbiota transplantation (FMT) experiment. Thirty-two women were randomized to RYGB (n = 16) or RYGB plus a 6-month exercise training program initiated three months post-surgery (RYGB + ET; n = 16), while a lean control group (LEAN; n = 16) was evaluated at baseline. Blood and fecal samples were collected before surgery, and at 3 (POST3) and 9 (POST9) months following surgery for biochemical, inflammatory, and microbiota analyses. Both surgical groups showed comparable improvements in body composition and inflammation; however, RYGB + ET was associated with greater improvements in HDL, triglycerides, fasting glucose, and fasting insulin. Exercise was also associated with increased gut microbiota α-diversity and shifts in microbial composition, including enrichment of genera previously linked to short-chain fatty acid (SCFA) metabolism and host metabolic health. To explore the potential contribution of these microbial communities, fecal microbiota collected at POST9 were transplanted into 36 high-fat diet-fed female mice, generating recipient groups rRYGB, rRYGB+ET, and rLEAN. Mice receiving RYGB + ET microbiota displayed similar inflammatory status and glucose tolerance, but lower fasting insulin and HOMA-IR, along with partial preservation of intestinal morphology, compared with mice receiving RYGB microbiota. These findings suggest that exercise following bariatric surgery is associated with distinct gut microbial configurations and metabolic improvements, and that exercise-conditioned microbiota may contribute to aspects of host metabolic regulation after surgery.
Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. To evaluate the longitudinal association of pancreatic fat with incident type 2 diabetes (T2D) and glycemic progression, with exploratory narrative synthesis of evidence in lean populations. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 1, 2026. Longitudinal observational studies assessing pancreatic fat at baseline and reporting subsequent incident T2D, glycemic progression, or both were included. Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the Newcastle-Ottawa Scale. Ten studies were included. In the primary binary meta-analysis (5 studies), higher pancreatic fat burden was associated with incident T2D (pooled effect estimate, 2.56; 95% CI, 1.27-5.14; I2 = 93.3%). Exclusion of 1 influential ultrasound-based study attenuated heterogeneity while preserving the association (pooled effect estimate, 1.45; 95% CI, 1.23-1.73; I2 = 10.2%). A separate continuous analysis (3 studies) also supported an association with incident T2D (1.17; 95% CI, 1.04-1.32; I2 = 79.2%), although exposure scales were not directly comparable. Pancreatic fat was also associated with glycemic progression (2 studies; 1.96; 95% CI, 1.10-3.48; I2 = 73.2%). Exploratory lean-population evidence was limited to 2 analytical contexts, synthesized narratively, and directionally consistent with the overall findings. Pancreatic fat was associated with adverse future glycemic outcomes across multiple analytical contexts. These findings support pancreatic fat as a potentially meaningful imaging-derived marker of future dysglycemia, while suggesting that heterogeneity is partly explained by differences in exposure ascertainment.
White adipose tissue (WAT) plays a central role in maintaining systemic metabolic homeostasis by buffering lipid flux throughout the body. Impairment of this lipid-buffering capacity is a hallmark of obesity and has also been observed during chronic viral infection. Such dysfunction is closely associated with ectopic fat accumulation, particularly in the liver. We hypothesized that the coexistence of obesity and chronic viral infection exacerbates WAT dysfunction, thereby promoting liver pathology. However, the specific response of obese WAT to chronic viral infection - and its downstream impact on liver health - remains to be explored. To investigate this interaction, we employed a model of chronic viral infection in mice using lymphocytic choriomeningitis virus (LCMV) clone 13. In obese hosts, chronic infection caused sustained WAT depletion and progressive weight loss, accompanied by a reduction of Tim-4+ eWAT-resident macrophages and features reminiscent of lipodystrophy and aggravated metabolic dysfunction-associated steatotic liver disease (MASLD). Depletion of CD8+ T cells, the key mediators of LCMV-driven weight loss in lean mice, only modestly attenuated weight loss and did not ameliorate liver pathology in obese mice. Likewise, therapeutic interventions including TNF-α blockade and glycemic control with metformin did not reverse infection-induced weight loss; moreover, TNF-α blockade failed to improve liver pathology. Collectively, these findings reveal a previously unrecognized crosstalk between WAT and the liver in infection-driven MASLD, highlight distinct responses in WAT of obese mice compared to their lean counterpart, and underscore the increased susceptibility to virus-induced metabolic complications in obesity.
1. Indigenous poultry breeds, like Kadaknath and Aseel, represent invaluable genetic resources, combining unique nutritional and cultural traits. The Kadaknath breed is famed for its black, lean, iron-rich meat with high protein and antioxidant content, while Aseel is a muscular breed prized for endurance, stress tolerance and fighting abilities. Despite their economic and nutritional value, the genetic and metabolic underpinnings of their distinct traits remain underexplored.2. This study conducted a comparative transcriptomic analysis of liver tissue from Kadaknath and Aseel chickens using RNA sequencing (RNA-seq) to uncover the molecular mechanisms driving their phenotypic diversity. The results identified 435 differentially expressed genes (DEG) linked to key processes such as lipid metabolism, oxidative phosphorylation and stress response.3. In Kadaknath chickens, up-regulated genes, including CPT1A, PCK1, TXNRD3 and PPARGC1A, were associated with efficient triglyceride breakdown, strong antioxidant defence and optimised energy metabolism. This likely contributes to the characteristic lean, nutrient-rich meat with high protein and low fat content.4. In contrast, Aseel birds showed elevated expression of stress response genes (MRPL18 and RPL11) and mitochondrial genes (NDUFA1, NDUFA8, NDUFB9 and PTPMT1), supporting its high energy requirements and resilience to stress, crucial for its endurance as a fighter breed. Gene co-expression network analysis highlighted critical hub genes driving these breed-specific adaptations.
Overweight and obesity are prevalent health concerns among postmenopausal women. However, the effects of aerobic exercise training on multidimensional body composition outcomes in postmenopausal women with overweight or obesity, as well as the potential dose-response relationship, remain unclear. This systematic review and meta-analysis followed PRISMA guidelines. PubMed, Cochrane Library, Web of Science, EBSCO, and ProQuest were searched from inception to March 8, 2026. Randomized controlled trials comparing aerobic exercise training with non-exercise control in postmenopausal women with overweight or obesity were included. Three-level meta-analyses were performed to account for dependent effect sizes. Restricted cubic spline models, subgroup analyses, and meta-regression were used to explore dose-response patterns and potential moderators. Sixteen RCTs involving 1,571 participants were included. Compared with non-exercise control, aerobic exercise training reduced body weight (MD = -2.17 kg, P < 0.01; low certainty), body mass index (MD = -0.73 kg/m2, P < 0.01; low certainty), body fat percentage (MD = -1.40%, P < 0.01; moderate certainty), fat mass (MD = -1.83 kg, P < 0.01; moderate certainty), waist circumference (MD = -2.02 cm, P < 0.01; moderate certainty), and hip circumference (MD = -1.39 cm, P = 0.04; low certainty). The pooled estimate for lean body mass was positive but imprecise (MD = 0.72 kg, P = 0.14; low certainty). Baseline age was inversely associated with changes in body weight and BMI. No clear non-linear dose-response association was observed between total aerobic exercise volume and pooled body composition effects, although some fitted curves suggested possible plateau-like patterns. Aerobic exercise training may improve several adiposity-related body composition outcomes in postmenopausal women with overweight or obesity, although the evidence for hip circumference and lean body mass remains less certain. Future trials should improve reporting of exercise dose, adherence, dietary control, and follow-up outcomes.