Cancers doi: 10.20517/mtod.2025.180

Authors: Xiaotao Li,Feifei Shao,Lianping Zhao,Chongkui Sun,Cuixia Gao,Limin Tian

Aim: Subclinical hypothyroidism (SCH) may be associated with cognitive impairment, and disruptions in bile acid (BA) metabolism are implicated in cognitive impairment-related diseases. However, the role of BA metabolism in SCH-related mild cognitive impairment (MCI) is not well understood. This study aimed to evaluate plasma BA levels in SCH patients with and without MCI using targeted metabolomics to explore potential metabolic changes linked to cognitive impairment.

Methods: A cross-sectional observational study enrolled 38 newly diagnosed adult-onset primary SCH patients with MCI (SCH-MCI), 35 patients with normal cognition (SCH-NC), and 41 well-matched healthy controls (HCs). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Plasma BA levels were quantified using targeted metabolomics via liquid chromatography-tandem mass spectrometry. Analysis of variance was employed to identify differential BAs, while Spearman correlation analysis was used to evaluate relationships between differential BAs, thyroid function parameters and MoCA scores. Receiver operating characteristic (ROC) analysis was conducted to identify sensitive BA markers for distinguishing SCH-MCI from SCH-NC.

Results: SCH-MCI patients exhibited significantly elevated levels of allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), glycodeoxycholic acid, taurodeoxycholic acid, and the ratio of alloLCA to chenodeoxycholic acid compared to SCH-NC patients. Negative correlations were found between alloLCA, isoLCA and MoCA scores. ROC analysis indicated that alloLCA and isoLCA could differentiate SCH-MCI from SCH-NC with high diagnostic accuracy.

Conclusion: Our study suggests that altered plasma secondary BA levels in SCH-MCI are negatively associated with cognitive function, highlighting the potential role of BA metabolism in SCH-related cognitive impairment.

Cancers doi: 10.20517/mtod.2025.212

Authors: Yishan Ma,Bixuan Tang,Yingjuan Zeng,Yingying Zhan,Li Cong,Fang Hu

Aim: To explore the impact of once-weekly semaglutide-induced weight loss on regional body composition in overweight or obese adults.

Methods: This retrospective cohort study enrolled 47 overweight or obese adults (body mass index ≥ 30 kg/m², or ≥ 27 kg/m² with ≥ 1 weight-related comorbidity). Participants received once-weekly semaglutide (initiated at 0.25 mg and gradually escalated to 2.0 mg) for 12 weeks, along with lifestyle intervention. The primary outcome was the change in regional body composition from baseline to week 12, which was measured using dual-energy X-ray absorptiometry.

Results: Semaglutide combined with lifestyle intervention resulted in a significant reduction in body weight (-6.77 ± 4.85 kg, P < 0.001), comprising a 4.75 kg (70.16%) loss of fat mass and a 2.02 kg (29.84%) reduction in muscle mass. The rate of visceral fat reduction was 5.16 percentage points greater than that of subcutaneous fat (21.25% vs. 16.09%; P = 0.009). With the exception of muscle mass in the right arm, both fat mass and muscle mass decreased in all other regions (all P < 0.008). The absolute reductions in fat mass, listed in descending order, were as follows: left leg (-0.74 kg), right leg (-0.71 kg), gynoid (-0.72 kg), android (-0.63 kg), left arm (-0.26 kg), and right arm (-0.19 kg). Similarly, the absolute reductions in muscle mass, in descending order, were: left leg (-0.54 kg), right leg (-0.48 kg), gynoid (-0.43 kg), android (-0.19 kg), left arm (-0.19 kg), and right arm (-0.08 kg). The muscle-to-fat ratio increased in all regions (all P < 0.008). Furthermore, multiple metabolic parameters improved concurrently.

Conclusion: Semaglutide, combined with lifestyle intervention, significantly reduces body weight, improves body composition, and enhances metabolic profiles. Future studies will further validate these findings by increasing the sample size, including parallel control groups, and extending the treatment and follow-up periods.

Cancers doi: 10.20517/mtod.2025.226

Authors: Zhitong Li,Angxian Lü,Wenxia Ren,Wenjing Wang,Boya An,Xiaoying Fan,Yuanyuan Yan,Yajing Bai,Anqi Zhao,Ruixue Duan,Shiwei Liu

Aim: Cardiometabolic multimorbidity (CMM) is increasingly prevalent in China’s aging population, posing major public health challenges. Developing machine learning (ML) models for early prediction is essential to inform prevention.

Methods: We used data from 16,970 adults aged ≥ 45 years from the China Health and Retirement Longitudinal Study (CHARLS) across four waves (2011-2018). We used 42 predictors from 2013/2015 (demographics, lifestyle factors, physical measures, and blood biomarkers) to train five ML models: generalized linear model (GLM), gradient boosting machine (GBM), distributed random forest (DRF), deep learning (DL), and a Stacked Ensemble model. The primary outcome was CMM in 2018, defined as self-reported diagnoses of ≥ 2 conditions among hypertension, diabetes, heart disease, and stroke. Models were evaluated using the area under the curve (AUC), Brier score, and calibration curves. Synthetic Minority Over-sampling Technique (SMOTE) and 5-fold cross-validation were used to optimize performance.

Results: The Stacked Ensemble model achieved the best internally validated predictive performance (AUC = 0.755), significantly outperforming GLM and DL (both DeLong’s P = 0.03), with comparable performance to GBM and DRF. Calibration analysis confirmed reliable prediction (Brier score = 0.153). Variable importance analysis based on GBM and DRF identified dyslipidemia, age, triglycerides, high-density lipoprotein cholesterol, waist circumference, self-rated health expectations, pain, cooking fuel type, weight change, and cystatin C as the top-ranked predictors common to both algorithms.

Conclusion: ML algorithms, particularly ensemble models, can effectively predict CMM risk in China’s aging population. The integration of diverse health indicators and self-perceived health measures enhances predictive power.

Cancers doi: 10.20517/mtod.2025.231

Authors: Zhitong Li,Yuanyuan Yan,Wenjing Wang,Boya An,Xiaoying Fan,Yajing Bai,Angxian Lü,Anqi Zhao,Ruixue Duan,Shiwei Liu

Aim: Estimated pulse wave velocity (ePWV) is a validated measure of arterial stiffness. While linked to cardiovascular disease, its longitudinal relationship with domain-specific cognitive decline in the general ageing population remains to be fully established.

Methods: We studied 5,080 participants (median age 64.0 years) from the English Longitudinal Study of Ageing (waves 2-9, 2004-2019). Baseline ePWV was calculated from age and mean blood pressure. Cognitive function (global, memory, executive, orientation) was assessed biennially. We used multivariable-adjusted linear mixed models to examine associations between baseline ePWV (natural log-transformed) and the rate of cognitive decline across a median follow-up duration of 10.1 years.

Results: In cross-sectional analysis, higher baseline ePWV was linked to poorer cognitive scores across all domains (all P < 0.001). Longitudinally, each unit increase in log-ePWV was linked to an accelerated annual decline in global cognitive score (-0.024 points/year; 95% confidence interval (CI) -0.026 to -0.021), memory (-0.022; -0.024 to 0.019), executive function (-0.019; -0.022 to -0.016), and orientation (-0.017; -0.021 to -0.013). A distinct dose-response pattern was evident: compared to the lowest quartile, participants in the highest ePWV quartile experienced the fastest decline in global cognition (-0.128 points/year), memory (-0.118/year), and executive function (-0.102/year) (P for trend < 0.001).

Conclusion: Higher arterial stiffness, as measured by ePWV, is independently linked to accelerated long-term decline across diverse cognitive domains in community-dwelling older adults. ePWV may be a useful vascular biomarker linked to increased cognitive decline risk, requiring confirmation in prospective studies.

Cancers doi: 10.20517/mtod.2025.139

Authors: Dongsen Hu,Rumeng Tang,Yayun Wang,Xing Hang,Ling Zhou,Yu Wei,Run Lin,Runze Wang,Lili Zhang,Linhua Zhao

Aim: Diabetic kidney disease (DKD) is a serious complication of diabetes, whose precise pathogenesis remains incompletely understood. Identifying therapeutic targets of DKD remains of great importance.

Methods: Four independent DKD microarray datasets were analyzed to identify differentially expressed genes. The expression quantitative trait locus (eQTL) data and DKD data from Genome-Wide Association Studies (GWAS) were utilized for Mendelian randomization (MR) analysis to pinpoint genes associated with DKD. The intersection of genes derived from two approaches was identified as key genes for DKD. Key genes were then subjected to enrichment analyses, immune infiltration assessment. Colocalization analysis, and quantitative polymerase chain reaction (qPCR) validation were used to identify core genes. A human DKD single-cell RNA sequencing dataset was analyzed to validate the cell-type-specific expression patterns of the core genes.

Results: We identified 275 up- and 184 downregulated genes. Combined with MR, seven key genes were determined. They were involved in lipid metabolism, protein secretion, signal transduction, immune response, and fibrosis. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) analysis revealed the unique distribution of immune cells in DKD and the regulation of immune cells by key genes. Colocalization analysis indicated a strong association between cystatin A (CSTA), lipoprotein lipase (LPL), lysozyme (LYZ), transforming growth factor beta induced (TGFBI), interferon induced protein with tetratricopeptide repeats 1 (IFIT1), and DKD. The qPCR confirmed that CSTA, LYZ, and TGFBI were differentially expressed, serving as core genes. LYZ was the most crucial. Single-cell analysis further unmasked the specific upregulation of CSTA, LYZ, and TGFBI in macrophages, where simulated knockout suggested a regulatory role in restraining antigen presentation.

Conclusion: This study demonstrated the potential and underlying mechanisms of gene-targeted therapy for DKD, providing a foundation for future investigations.

Cancers doi: 10.20517/mtod.2025.210

Authors: Weihan Zhang,Jing Xue,Jianjun Wang,Dongdong Ni,Wenjing Zhou,Bin Wang,Jinyi Shi,Aihong Wang

Aim: This study investigated the effects of semaglutide combined with metformin on body weight, glucose and lipid metabolism, sex hormone levels, menstrual cyclicity, and psychological parameters of women living with polycystic ovary syndrome (PCOS)-related infertility and overweight/obesity.

Methods: Sixty-four patients living with infertility and PCOS [body mass index (BMI) ≥ 24 kg/m²] were randomly assigned to standard (n = 32) or semaglutide-intensified treatment groups (n = 32). Both groups underwent lifestyle modification interventions. The standard group received metformin monotherapy [500 mg three times daily (TID)] for 12 weeks, whereas the semaglutide-intensified treatment group received metformin and semaglutide for 12 weeks. An 8-week washout period followed treatment.

Results: The semaglutide-intensified treatment group showed a higher percentage of patients with restored menstrual cycles (86.87% vs. 60.00%, P = 0.038). Significant reductions in luteinizing hormone (LH), androgen levels, and the LH/follicle-stimulating hormone ratio were observed. Greater reductions were also noted in BMI, waist and hip circumference, absolute weight loss, body fat percentage, fasting plasma glucose, fasting insulin, and Homeostatic Model Assessment of Insulin Resistance (P < 0.05). No significant differences were observed in total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Psychological distress was not exacerbated in the semaglutide-intensified treatment group.

Conclusion: In women living with PCOS-related infertility and overweight/obesity, semaglutide combined with metformin provided superior improvements in weight reduction, glucose metabolism, insulin sensitivity, and menstrual cyclicity compared with metformin monotherapy, without exacerbating psychological distress. These findings suggest that semaglutide represents a promising therapeutic option for the clinical management of this population.

Cancers doi: 10.20517/mtod.2025.222

Authors: Ralf Weiskirchen,Amedeo Lonardo

Ancient mythology alluded to the liver’s regenerative capabilities, a phenomenon now validated by scientific research: the organ can regenerate up to 75% of its mass following partial resection, provided sufficient tissue remains. This commentary synthesizes and contextualizes a recent review article that emphasizes lipid metabolism as a key component of liver regeneration. Effective regeneration depends on the viability of hepatocytes, contributions from supporting cells, metabolic adaptability, and appropriate management of infections and hemodynamics. The regenerative process unfolds in distinct phases: cytokine priming, cellular proliferation, and termination. In cases of acute injury, hepatocytes are primarily responsible for regeneration, whereas in chronic disease states, progenitor-like cells also contribute. Recovery is influenced by hormonal status, nutritional state, age, and signals from non-parenchymal cells, with zone 2 hepatocytes playing a pivotal role. Lipid metabolism is critical; moderate lipid accumulation supports regeneration, whereas excessive fat deposition hinders it. Lipophagy provides essential energy and mitigates toxicity, while endoplasmic reticulum (ER) stress must be properly regulated. Therapeutic strategies focus on optimizing β-oxidation, enhancing lipophagy, and managing ER stress, guided by lipid profiling and fat quantification. Personalized interventions tailored to phase-specific lipid metabolic needs may optimize liver regenerative outcomes.

Cancers doi: 10.20517/mtod.2026.03

Authors: Zhitong Li,Haiyan Li,Haoran Gong,Hua Yang,Linlin Gao,Xuhui Li,Anqi Zhao,Wenjing Wang,Yuanyuan Yan,Shiwei Liu

The global epidemic of dysglycemia, spanning from pre-diabetes to overt type 2 diabetes (T2D), constitutes a primary driver of cardiovascular morbidity and mortality worldwide. While managing established T2D remains crucial, accumulating evidence underscores that the pre-diabetic state itself represents a period of active, subclinical cardiovascular injury. This commentary argues for a fundamental strategic shift: from merely delaying progression to T2D toward actively pursuing remission of pre-diabetes - defined as the sustained return to normoglycemia - as a potent and likely essential target for curbing cardiovascular disease. This approach moves beyond traditional risk factor management by targeting a reversible pathophysiological nexus. The rationale is robust, implicating insulin resistance, hyperinsulinemia, β-cell stress, chronic inflammation, endothelial dysfunction, and a pro-atherogenic lipid profile. Notably, long-term follow-up data from landmark prevention trials now provide compelling evidence that achieving remission is associated with a striking reduction of approximately 50% in the risk of cardiovascular death and heart failure hospitalization. Although intensive lifestyle intervention remains the cornerstone, emerging therapeutic options - including potent glucagon-like peptide-1 (GLP-1) receptor agonists, glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonists, and metabolic surgery - offer new pathways to induce remission. Nevertheless, significant gaps persist, primarily the lack of a consensus definition for pre-diabetes remission and the absence of prospective trials with remission as a primary cardiovascular endpoint. Addressing these gaps through coordinated research, consensus-building, and integration into clinical guidelines is imperative to translate this paradigm from a compelling hypothesis into a standard of care capable of altering the cardiovascular trajectory of hundreds of millions at risk.

Cancers doi: 10.20517/mtod.2025.195

Authors: Richard Gill,Taiyi Kuo

Recent advances in obesity and type 2 diabetes treatment using glucagon-like peptide-1 receptor agonist (GLP1RA)-based therapeutics have enabled major improvements in the management of these metabolic disorders. However, many patients cannot tolerate side effects associated with appetite suppression, and around 10% of those adhering to treatment do not lose weight. Thus, there is a need for alternative and/or additional treatment. Here, we examine the therapeutic potential of targeting a gene called Group-specific component (GC) to treat metabolic diseases. First, we review GC’s established roles in vitamin D transport, metabolism, and inflammation, including its structure-activity relationships as well as the phenotypes associated with genetic variation in GC. Next, we summarize studies of GC-null humans and mice, which were both generally healthy and viable, demonstrating the safety of inhibiting GC. Finally, we discuss novel evidence that among mice fed a high fat diet, Gc ablation confers protection against the development of obesity and type 2 diabetes. Notably, these benefits came without reductions in food intake or lean mass, the primary drivers of GLP1RA-associated adverse effects. GC therefore represents a promising novel therapeutic target for metabolic diseases.

Cancers doi: 10.20517/mtod.2025.191

Authors: Hui Jiang,Shan Tang,Chen Liang,Hui Liu,Haitian Yu,Siqi Zhang,Meihan Li,Yue Wang,Wei Hou,Sujun Zheng

Aim: To investigate the clinical relevance of autoimmune phenomena (AP), including autoantibody positivity and elevated serum immunoglobulins, in patients with Wilson’s disease (WD), particularly with respect to disease severity and prognosis.

Methods: We retrospectively enrolled treatment-naïve WD patients (Leipzig score ≥ 4) and classified them as WD with AP (AP-WD) or WD without AP (NAP-WD) based on autoantibody positivity (titer ≥ 1:100) and/or immunoglobulin G (IgG) above the upper limit of normal. Baseline laboratory data, clinical complications, and liver histopathology were compared. Patients received standard anti-copper therapy and were followed longitudinally to evaluate the impact of AP on liver-related outcomes.

Results: Eighty-six treatment-naïve WD patients were included (48 AP-WD, 38 NAP-WD). At baseline, AP-WD patients exhibited more severe laboratory and clinical features, including lower platelet counts, reduced albumin, prolonged international normalized ratio, higher aspartate aminotransferase-to-platelet ratio index (APRI), Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD), and Child-Pugh scores, and greater prevalence of ascites (all P < 0.05). Histopathological analysis demonstrated increased plasma cell infiltration and heightened portal inflammatory activity in the AP-WD group (P < 0.05). Longitudinal follow-up revealed that the presence of AP was independently associated with an increased risk of adverse liver-related events, including liver transplantation, or death.

Conclusion: AP is common in WD and correlates with more severe hepatic dysfunction and poorer long-term outcomes. Screening for autoantibodies and IgG levels in newly diagnosed WD patients may provide important prognostic insight and facilitate early risk stratification, guiding tailored monitoring and management strategies.

Cancers doi: 10.20517/mtod.2025.146

Authors: Jie Wang,Jingjing Zeng,Wenjuan Yang,Bo Chen,Menglin Fan,Zhaoxia Zhang,Ying Xing,Shaoyong Xu

Aim: The study aims to explore the relationship between objectively measured physical activity (PA) timing and the cardiovascular disease (CVD) incidence, cardiovascular-specific mortality, and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients.

Methods: Data were obtained from the UK Biobank, a population-based prospective cohort study. From February 2013 to December 2015, the PA of the participants was objectively measured by continuously wearing an accelerometer for 7 days. CVD was defined through the International Classification of Diseases (10th Revision) codes by linking to national hospitalization data. Death data was obtained through the National Health Service Information Center. K-means cluster analysis was used to cluster patients with similar temporal activity patterns.

Results: Among 3,143 adults with T2DM (mean age 65.9 years; 62.0% men), followed for a median of 7.82 years, 13.91% developed CVD, 13.53% died from cardiovascular causes, and 9.61% died from any cause. A Cox proportional hazards regression model showed that higher hourly PA was associated with lower CVD and cardiovascular mortality risk, particularly for activity accumulated between 8 am and 4 pm. Lower ACM risk was observed for activity performed throughout the day and evening, whereas elevated early-morning activity, most notably around 3 am, was linked to higher CVD and mortality risk. Cluster analysis identified three PAtiming profiles. Compared with participants exhibiting evenly distributed daytime activity (Cluster 1), those with morning activity peaks at 8-9 am (Cluster 2) or 11-12 am (Cluster 3) had substantially reduced CVD incidence {hazard ratio (HR) 0.449 [95% confidence interval (CI), 0.318-0.634] and 0.493 (95%CI: 0.363-0.670), respectively}. The ACM risk was similarly lower in clusters 2 [HR 0.625 (95%CI: 0.448-0.873)] and 3 [HR 0.548 (95%CI: 0.403-0.746)]. These associations were independent of overall PA intensity.

Conclusion: Engaging in PA in the late morning or at noon is associated with a lower risk of CVD and ACM in patients with T2DM. Time-dependent PA interventions may constitute an additional benefit for managing cardiovascular and mortality risks in these patients.

Cancers doi: 10.20517/mtod.2025.193

Authors: Amedeo Lonardo,Mohamad Jamalinia,Ralf Weiskirchen

Metabolic dysfunction-associated steatotic liver disease (MASLD) defines the metabolic origin of ectopic accumulation of intrahepatic fatty substrates that affect multiple organ systems. Given the key role of sex in metabolic regulation, this article reviews sex-specific disparities in the epidemiology, pathomechanisms, clinical course, and therapeutic responses associated with MASLD. The influence of reproductive health on the risk of disease in males and females is also examined. Although MASLD is more prevalent in males, the protective effect observed in females diminishes following menopause, highlighting the significant roles that biological sex and reproductive status play in disease progression. Women may face an elevated risk of certain MASLD-related extra-hepatic complications, and ongoing research is elucidating the mechanisms underlying these sex disparities. Biological sex modifies MASLD susceptibility through diverse factors, including fat distribution, adipose tissue pathobiology, hormone signaling pathways, gene-hormone interactions, immune system dynamics, and bile acid composition. Menstrual and reproductive factors, as well as exogenous hormone exposure, further contribute to differential risk profiles. Both endogenous hormone concentrations and sex chromosome composition are relevant for liver health, as evidenced by increased susceptibility in conditions such as polycystic ovary syndrome and certain chromosomal aneuploidies. The review further discusses MASLD in the context of pregnancy and lactation and examines sex-based variation in response to lifestyle modification and pharmacological therapy. Finally, recommendations for future research directions are provided.

Cancers doi: 10.20517/mtod.2025.154

Authors: Bofei Zhang,Bingrui Gao,Jie Zheng,Jing Li

Prenatal environmental exposure is a significant factor in childhood obesity, and the underlying mechanisms of its multidimensional environmental factors are receiving increasing attention. While existing research has primarily focused on the obesity-promoting effects of individual environmental factors, comprehensive evidence on the combined impact of complex exposure systems, including endocrine-disrupting chemicals (EDCs), air pollutants, maternal metabolic abnormalities, and adverse lifestyle choices, remains to be consolidated. This review systematically examines the combined effects of intrauterine EDCs, air pollutants, maternal metabolic abnormalities, and adverse lifestyle factors on the risk of childhood obesity. It summarizes the mechanisms through which these factors interfere with fetal energy balance programming via shared pathways, including epigenetic alterations, placental dysfunction, and metabolic inflammation. The aim is to construct a multidimensional spectrum of environmental exposures during early life, providing a theoretical basis for the early stratification of risk and the precise prevention and control of childhood obesity.

Cancers doi: 10.20517/mtod.2025.105

Authors: Angelo Di Vincenzo,Marnie Granzotto,Marika Crescenzi,Federico Capone,Paola Fioretto,Marco Rossato

It has long been debated whether targeting systemic inflammation can lessen the burden of obesity-related cardiometabolic complications. In the cardiovascular field, various pharmacological approaches using anti-inflammatory agents as preventive strategies have been conducted, but results have been mixed. In this context, understanding the pathophysiology of meta-inflammation remains incomplete, as the problem must be approached from multiple perspectives. The molecular pattern regulated by the purinergic receptor P2X7 and the subsequent activation of the inflammasome play a crucial role in inflammatory responses and could serve as a target. Specifically, the P2X7 receptor pathway appears to be involved in the development of cardiovascular, hepatic, and renal abnormalities associated with metabolic syndrome. In this review, we briefly outline the current state of knowledge and our perspective on the role of the P2X7 receptor in obesity and its related complications, as highlighted in the new definition of cardiovascular-kidney-metabolic syndrome. Since P2X7 receptor antagonists are currently under development, particularly for rheumatological diseases, this approach merits investigation in future translational studies, especially in combination with incretin-based therapies.

Cancers doi: 10.20517/mtod.2025.32

Authors: Pojsakorn Danpanichkul,Hanna Blaney,Javiera Perelli,Paula Huerta,Francisco Idalsoaga,Marco Arrese,Juan Pablo Arab,Rohit Loomba,Luis Antonio Díaz

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading global cause of chronic liver disease and is strongly linked to cardiovascular disease (CVD), which remains the primary cause of death in affected individuals. This narrative review summarizes contemporary evidence on the MASLD–CVD interface and outlines a practical framework for cardiovascular risk assessment and comorbidity management. We discuss how liver disease severity can inform cardiovascular risk stratification beyond traditional scores, including cardiovascular imaging, biomarkers of myocyte injury and stress, inflammation markers, proteomics, lipidomics, and lipid profiles. Lifestyle interventions - dietary optimization, weight loss, and increased physical activity - remain foundational and improve hepatic steatosis and key cardiometabolic parameters. Pharmacotherapies with relevance to MASLD and cardiometabolic disease - including β-selective thyromimetics, incretin-based therapies, sodium–glucose cotransporter 2 inhibitors, and pioglitazone - offer benefits across weight, glycemic control, and metabolic risk, while statins remain the cornerstone of dyslipidemia management and CVD prevention in MASLD. For patients who do not achieve lipid targets or are statin-intolerant, non-statin therapies such as proprotein convertase subtilisin/kexin type 9 inhibitors and bempedoic acid provide additional risk-reduction options. Bariatric surgery can achieve durable weight loss and meaningful improvements in steatohepatitis and fibrosis in carefully selected patients. Finally, we emphasize the need for integrated, multidisciplinary care pathways that coordinate hepatology, cardiology, endocrinology, and primary care to identify high-risk individuals early, tailor intensity of preventive therapies, and address the concurrent liver and CVD burden.