Search Results (2,506)

Multiple North American and European societies now endorse a combined serological and imaging-based clinical care pathway for non-invasive risk stratification of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A multidisciplinary group of Canadian radiologists, hepatologists, family physicians, and other health professionals have recently published consensus guidelines for identification and risk stratification of patients with suspected MASLD. Screening should be performed with the FIB-4 score, and those with an indeterminate FIB-4 (between 1.32.67) should undergo imaging-based liver stiffness evaluation either with transient elastography (FibroScan), ultrasound shear wave elastography, or magnetic resonance elastography as a second step. While the implementation of these techniques for measuring liver stiffness differ, there is no clinically significant difference in their diagnostic performance. This narrative review, intended for Family Physicians, summarizes recommendations for serological investigations and imaging modalities of liver steatosis and stiffness. Practical guidance includes an algorithm with thresholds. We discuss current challenges and future directions of risk-stratifying patients with MASLD in the community. Full article

Background: Fresh frozen tissues are considered the gold standard for proteomic analyses due to their superior preservation of protein integrity; however, their use is limited by the logistical and financial requirements of long-term cold storage. Formaldehyde-fixed paraffin-embedded (FFPE) tissues provide a practical alternative, owing to their stability and widespread availability in clinical settings. A critical step in FFPE proteomics is deparaffinization, which traditionally relies on organic solvents such as xylene, along with the efficient reversal of formaldehyde-induced crosslinks. Methods: In this study, we evaluated multiple FFPE protein extraction and digestion workflows including chaotropic, surfactant-based, and detergent-free approaches in combination with xylene-free deparaffinization strategies, using label-free data-independent acquisition (DIA) LC-MS/MS. Results: Among the tested methods, a chaotropic, reductant, and surfactant-free in-solution digestion workflow demonstrated robust protein and peptide recovery. A modified version of this protocol further improved peptide coverage while maintaining comparable protein depth. The applicability of the optimized workflow was assessed using FFPE needle biopsy samples from control, hepatic steatosis, and liver fibrosis groups. Exploratory proteomic patterns were observed across conditions, with hepatic steatosis associated with early activation of stress-response pathways, while fibrosis showed evidence suggesting altered lipid metabolism. Conclusions: Overall, this study presents a simple, xylene-free, and MS-compatible workflow for FFPE proteomics that is suitable for low-input clinical samples and may support broader application of archival tissues in proteomic research. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly associated with the development of cardiovascular disease (CVD); however, the mechanisms responsible are currently unknown. We have developed a model of MASLD due to the loss of hepatocyte peroxisome proliferator-activated receptor α (PPARα^HEPKO). We found that plasma beta-hydroxybutyrate (BHOB) levels were significantly reduced in PPARα^HEPKO mice and aimed to investigate the therapeutic potential of restoring BHOB levels in the development of CVD in these mice. Thirty-week-old PPARα^HEPKO and control PPARα^FL/FL mice were randomized to receive 1,3 butanediol (1,3-BDO), a precursor of BHOB, in drinking water for 6 weeks. 1,3-BDO treatment resulted in a significant increase in plasma BHOB levels, a significant decrease in mean arterial blood pressure, improvement in systolic and diastolic function, a decrease in vascular stiffness, and improved exercise performance in PPARα^HEPKO mice. 1,3-BDO treatment did not alleviate hepatic steatosis in PPARα^HEPKO mice; however, it improved plasma cholesterol levels and decreased cardiac lipid accumulation, fibrosis, and apoptosis. 1,3-BDO treatment also resulted in a significant increase in cardiac AMP-activated protein kinase (AMPK) levels. Increasing plasma BHOB levels reverses CVD in our mouse model of MASLD. A similar approach could be an effective strategy for preventing the development of CVD in patients with human MASLD. Full article

Background: Clostridioides difficile infection (CDI) remains a leading cause of hospital-acquired infection. Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and has been associated with increased infectious susceptibility. However, whether non-cirrhotic MASLD independently worsens inpatient CDI outcomes and whether this differs across the MASLD spectrum remain unclear. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) 2017–2023, identifying adult hospitalizations with a principal diagnosis of CDI. Patients with cirrhosis and alcoholic liver disease were excluded. Propensity score matching (1:1) was performed for the primary MASLD vs. non-MASLD comparison in the principal-diagnosis CDI cohort. To evaluate whether outcomes differ across the MASLD spectrum, survey-weighted multivariable logistic regression was used to compare K76.0-coded (MASLD without steatohepatitis) and K75.81-coded (MASH) hospitalizations against non-MASLD/MASH hospitalizations within the principal-diagnosis CDI cohort. The primary outcome was in-hospital mortality; secondary outcomes included complications, healthcare utilization, and discharge disposition. Results: The principal-diagnosis CDI cohort comprised 76,103 discharges (weighted ~380,515). MASLD prevalence among non-cirrhotic CDI hospitalizations nearly doubled from 1.98% in 2017 to 3.74% in 2023 (OR per year 1.089; p < 0.001). After propensity score matching (1756 pairs), MASLD was not associated with significantly higher in-hospital mortality (OR 1.252; p = 0.574) or most adverse outcomes, but was associated with lower odds of non-routine discharge (OR 0.794; p = 0.003). In the matched utilization analysis, length of stay and total charges were not significantly different, although the adjusted pre-match analysis showed higher charges among MASLD hospitalizations (+$4431; p = 0.001). Within the same principal-diagnosis cohort, K76.0-coded MASLD (n = 1988) was associated with lower odds of acute kidney injury (aOR 0.821; p = 0.004) and non-routine discharge (aOR 0.805; p = 0.001). K75.81-coded MASH (n = 197) was independently associated with higher in-hospital mortality (aOR 2.840, 95% CI 1.154–6.985; p = 0.023) and peritonitis (aOR 4.136, 95% CI 1.543–11.082; p = 0.005), although confidence intervals were wide and the number of MASH-coded hospitalizations was modest. Conclusions: The prevalence of MASLD among CDI hospitalizations is rising. Non-cirrhotic MASLD without steatohepatitis does not independently worsen inpatient CDI outcomes after adjustment, whereas K75.81-coded MASH may identify a higher-risk subgroup with increased mortality and peritonitis, pending confirmation in larger cohorts. These findings suggest that hepatic inflammatory activity, rather than steatosis alone, may drive adverse CDI outcomes and support further investigation of MASLD phenotyping in CDI risk stratification. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant and escalating global health concern, with an estimated prevalence of 30%. Current assessments of hepatic steatosis, a hallmark of MASLD, rely on semi-quantitative grading by pathologists, which is inherently limited by inter-observer variability. Objective: To address this limitation, we developed a novel deep learning pipeline, named SteatoStat, to standardize and enhance the quantification of hepatic steatosis in patients with MASLD. Method: The SteatoStat pipeline employs and integrates multiple components such as file format standardization, rule-based cell filtering, and multiple segmentation models across various liver structures, resulting in an output of a continuous quantitative measure of steatosis percentage and translated into steatosis grades. Results: We report a high degree of accuracy and reliability with SteatoStat achieving the following performance metrics (DICE score = 0.8955, AUROC = 0.9928, F1 score = 0.8990). When benchmarked against expert pathologists, the weighted Kappa coefficient is 0.837. Furthermore, in comparison with an existing, well-established model, SteatoStat demonstrated a weighted Kappa coefficient = 0.765. Conclusions: These robust findings underscore its potential clinical utility in providing a standardized objective quantification of hepatic steatosis. Future directions include enhancing the model’s generalizability and its clinical integration through validation on independent, multi-institutional datasets. Full article

Heat stress leads to excessive hepatic lipid deposition and oxidative imbalance in laying hens, especially during peak laying period. Chlorogenic acid (CGA), a dietary polyphenol with antioxidant and lipid-modulating properties, may improve hepatic lipid homeostasis, yet its effects under heat-stress conditions remain unclear. In this study, 240 Hy-Line Brown laying hens at 36 weeks of age were randomly assigned to one of two treatments (120 hens per treatment, with six replicates of 20 hens each): a basal diet or a basal diet supplemented with 300 mg/kg CGA and subjected to heat-stress conditions for 8 weeks. CGA supplementation significantly reduced liver weight (25.3%), liver index (14.4%), hepatic triglyceride content (29.1%), and serum triglyceride level (61.7%) (p < 0.05). Histological assessment revealed lower steatosis and inflammation scores, alongside increased hepatic SOD activity (13.6%) and decreased MDA content (58.7%) (p < 0.05). RNA-seq analysis identified 420 differentially expressed genes that were significantly enriched in PPAR signaling and fatty acid β-oxidation pathways. CGA upregulated fatty acid oxidation-related genes (ACSL1, CPT1A, ACOX1, ACAA1) and downregulated lipogenic markers (FASN, ACACA). Serum metabolomics revealed coordinated changes in lipid and carbon metabolism. These results indicate that dietary CGA alleviates hepatic lipid accumulation and oxidative stress in heat-stressed peak-laying hens, potentially via PPARα-mediated enhancement of fatty acid oxidation and inhibition of de novo lipogenesis. Full article

Background/Objectives: This study aims to estimate the prevalence of MASLD in a general outpatient population, describe associated metabolic risk factors, and evaluate liver fibrosis. Methods: We conducted a prospective, cross-sectional study at a tertiary hospital that included adults referred there for abdominal ultrasound for non-hepatic indications. Exclusion criteria were significant alcohol intake or known liver disease. Hepatic steatosis was assessed by ultrasound in all patients, and vibration-controlled transient elastography (VCTE) was performed in a subgroup. Clinical and laboratory data were collected. Comparisons used the chi-square test, Fisher’s exact test, and the Wilcoxon test, and logistic regression identified associated factors. Results: Hepatic steatosis was identified by ultrasound in 57.6% of the 182 patients, with most (93%) fulfilling the MASLD criteria. MASLD was diagnosed in 58.2% of patients based on ultrasound or VCTE findings of steatosis. Hepatic steatosis by ultrasound was associated with higher BMI (OR 1.30; 95% CI 1.18–1.43), hypertension (OR 1.92; 95% CI 1.04–3.53), glucose disorders (OR 3.33; 95% CI 1.60–6.92), and triglycerides (OR 1.01; 95% CI 1.00–1.03), while physical activity was protective (OR 0.86; 95% CI 0.26–0.99). Among 74 patients evaluated by VCTE, 8% had fibrosis (≥F1), which was more frequent in those with higher BMI and a number of cardiometabolic risk factors. Conclusions: This study reveals a high prevalence of MASLD and fibrosis among outpatients, supporting the use of abdominal ultrasound for opportunistic screening of MASLD and emphasizing the need for early risk stratification and referral. Full article

Fatty liver disease represents a major metabolic disorder affecting domestic animals worldwide, with significant implications for animal health, welfare, and agricultural productivity. Disrupted communication between mitochondria and other organelles—particularly the endoplasmic reticulum, lipid droplets, and lysosomes—plays a critical role in disease pathogenesis. This review synthesizes knowledge on inter-organellar communication across domestic animals, with emphasis on species-specific adaptations. We address the “Dairy Cow Paradox”—periparturient dairy cows develop severe hepatic steatosis (>30% liver fat), yet under sterile conditions, they have a higher threshold for progressing to sterile steatohepatitis compared to rodents and humans. However, it is critical to note that severe fatty liver in dairy cows is indeed associated with impaired autophagy, inflammation, and liver damage, particularly when accompanied by ketosis or concurrent infections, and 39% of transition cows exhibit moderate to severe lymphocytic hepatitis. We propose that the tolerance to severe steatosis in dairy cows arises from three adaptations: (1) attenuated innate immune sensing via the cGAS-STING pathway; (2) enhanced lipid buffering from perilipin 5 (PLIN5) with a hypothesized ruminant-specific Val152 substitution that may stabilize lipid droplet–mitochondria contacts; and (3) dampened calcium signaling due to ER–mitochondria membrane lipid raft rigidity, elevated inositol 1,4,5-trisphosphate receptor 2 (IP₃R2) expression, and reduced mitochondrial calcium uniporter (MCU) conductance. We contrast this with the inflammatory steatohepatitis common in rodent models driven by calcium overload and mitochondrial DNA (mtDNA) release, and glucocorticoid-mediated mitofusin 1 (MFN1) suppression, causing mitochondrial fragmentation in poultry. We identify critical knowledge gaps, including the need to define bovine and avian mitochondria-associated endoplasmic reticulum membrane (MAM) proteomes and spatially resolve hepatic zonal communication patterns. Targeting organellar communication hubs with nutraceuticals or pharmacological agents offers promising therapeutic strategies. Full article

Background/Objectives As a fat-soluble vitamin, vitamin E (VE) is prone to suboptimal intake in the general population. Alpha-tocopherol (α-TE) represents the most biologically significant form of VE in vivo. Nevertheless, the potential detrimental effects of α-TE deficiency on health remain unclear. This study was conducted to investigate the effect of α-TE deficiency on hepatic metabolism and gut microbiota. Methods C57BL/6J mice were randomly assigned to receive one of three dietary regimens: a α-TE-deficient diet, a control diet with normal α-TE, or a high-dose diet containing four times the normal α-TE level. Histopathology, serum biochemistry, RNA-Seq, RT-qPCR, Western blot, and 16S rRNA gene sequencing with correlation analysis were used to assess metabolic phenotypes, hepatic circadian, hepatic lipid metabolism, and cecal microbiota, respectively. Results The results demonstrated that α-TE deficiency induced hepatic steatosis and lipid metabolic disturbances. α-TE deficiency significantly decreased Arntl and Clock expression, but increased Per2. Additionally, it upregulated the expression of lipogenic genes such as Scd1, Elovl6, and Elovl3 and simultaneously downregulated fatty acid oxidation genes such as Cyp4a10, Cyp4a14, and Acot1, bringing about imbalance in lipid homeostasis. In addition, α-TE deficiency greatly changed the structure and composition of gut microbiota. Bacterial genera like Alistipes, norank_f__Muribaculaceae, Muribaculum, Odoribacter, and Dubosiella were significantly correlated with hepatic circadian and lipid metabolism gene expression with the strongest correlation being Alistipes. Conclusions This work is the first to reveal that short term α-TE deficiency could cause lipid metabolic disorder via the “gut microbiota–liver circadian clock” axis, which provides novel insights into the etiology of nutrition-related metabolic diseases and targets for nutritional intervention. Full article

Background: Vasomotor symptoms (VMS), particularly hot flashes and night sweats, are highly prevalent during the menopausal transition and have been increasingly associated with adverse cardiometabolic profiles. Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a major manifestation of systemic metabolic dysregulation and is rising globally. Emerging evidence suggests a potential overlap between menopausal symptom severity and MASLD risk; however, this relationship remains insufficiently characterized. Method: A scoping review was conducted in accordance with PRISMA-ScR guidelines to map the existing evidence on the association between VMS and MASLD. A comprehensive search of PubMed, Scopus, CINAHL, Cochrane Library, and MEDLINE was performed for English-language studies published between January 2015 and December 2025. Eligible studies included original research assessing both MASLD and menopausal symptoms. Data were extracted and synthesized narratively. Methodological quality was appraised using the CASP Cross-Sectional Studies Checklist. Results: Of 690 identified records, five cross-sectional studies met the inclusion criteria, comprising 106 to 5995 participants from Korea, Greece, and the United States. Across studies, moderate-to-severe VMS were consistently associated with increased MASLD prevalence or higher surrogate indices of hepatic steatosis. Women with more severe VMS demonstrated unfavorable metabolic profiles, including greater insulin resistance and elevated liver enzyme levels. Although adjustments for body mass index and hypertension attenuated some associations, the overall trend remained positive. Heterogeneity was observed in diagnostic tools and symptom assessment methods. Conclusions: Current evidence indicates a consistent association between VMS severity and MASLD in peri- and postmenopausal women. While causality cannot be inferred due to cross-sectional designs, VMS may represent a clinical marker of underlying metabolic and hepatic dysfunction. Longitudinal and mechanistic studies are warranted to clarify directionality and inform integrated screening strategies in midlife women. Full article

Background: Chronic exposure to artificial light at night (light pollution) causes circadian desynchronosis and melatonin deficiency, which is considered an independent driver of metabolic disorders and accelerated aging. However, the long-term effects of chronic desynchronosis on systemic metabolism and liver structure throughout the life cycle, as well as the potential of preventive melatonin administration, remain poorly understood. Objective: To evaluate the effects of chronic dark deprivation and prevention of metabolic disorders by exogenous melatonin on plasma melatonin levels, metabolic profile, liver function, and morphological changes in rats over a 24-month experiment. Methods: A 24-month experiment was conducted on 360 male Wistar rats divided into three groups: control (standard 10:14 h light/dark photoperiod), dark deprivation (DD, constant illumination), and correction (DD+Mel, constant illumination + melatonin 10 mg/kg five times per week). Animals were sacrificed at 6, 12, 18, and 24 months. Plasma melatonin was assessed by ELISA. Biochemical parameters (ALT, AST, LDH, total protein, albumin, bilirubin, glucose, triglycerides, and cholesterol), body weight, liver weight, relative liver weight, and histological parameters (steatosis, fibrosis, nuclear area, nuclear/cytoplasmic ratio, and binucleated hepatocytes) were analyzed. Results: In the DD group, a persistent progressive melatonin deficiency was detected (5.1-fold decrease by 6 months, p < 0.0005), accompanied by hypertriglyceridemia (Cohen’s d = 6.40), hypercholesterolemia (d = 4.59), biphasic dysglycemia (hypoglycemia followed by hyperglycemia), elevated ALT and AST activity (d = 2.60 and 2.46, respectively), hypoproteinemia (d = 5.33), hypoalbuminemia (d = 3.34), and hyperbilirubinemia (d = 3.22–4.37), as well as progressive steatosis (2.8 ± 0.3 points, d = 7.20) and pericellular fibrosis (1.8 ± 0.4 points, d = 4.50). In the DD group, a decrease in relative liver weight during the first 12 months was observed (metabolic disproportion, d = 2.31), reflecting disproportionate body weight gain. In the DD+Mel group, exogenous melatonin restored the biochemical parameters to values that did not differ statistically from the control values (Cohen’s d < 0.2 for most parameters), prevented steatosis (0.8 ± 0.3 points, d = 0.80) and fibrosis (0 points), increased relative liver weight by 24 months (3.83 ± 0.49 vs. 3.27 ± 0.029 in the control, d = 1.60), and increased the hepatocyte nuclear area (58.4 ± 4.1 vs. 48.6 ± 3.8 μm², d = 2.32). Conclusions: Chronic desynchronosis induced by constant illumination leads to persistent melatonin deficiency and complex metabolic and structural liver disturbances modeling accelerated aging. Exogenous melatonin (10 mg/kg five times per week) exhibits pronounced geroprotective, hepatoprotective, and antifibrotic effects, normalizing all biochemical parameters and preventing age-related liver involution. Full article

Micro- and nanoplastics (MNPs) are emerging environmental contaminants of increasing relevance to human health. Growing evidence suggests that, following ingestion, inhalation, or, less convincingly, dermal exposure, MNPs may cross biological barriers, enter lymphatic and vascular compartments, and reach the liver. Owing to portal blood flow, sinusoidal architecture and Kupffer cell activity, the liver appears to be one of the principal sites of early particle sequestration. Human biomonitoring, ex vivo and postmortem studies have detected MNPs in blood and multiple organs, including the liver, although the currently available evidence remains limited and methodologically heterogeneous. Their identification relies on multistep analytical procedures that integrate sample pretreatment with FTIR, Raman spectroscopy, LD-IR, Py-GC-MS and supplementary imaging methods. However, each of these techniques presents significant limitations, particularly in the analysis of nanoplastics. Experimental studies indicate that MNPs may induce hepatic injury through oxidative stress, mitochondrial impairment, endoplasmic reticulum stress, inflammation, DNA damage, dysregulated lipid metabolism and disruption of the gut–liver axis, consequently contributing to steatosis, cholestatic anomalies and fibrosis. Consequently, MNPs should be considered potential contributors to liver pathology, although more comprehensive human data are still required. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) is now recognized as a leading form of chronic liver disease globally and is strongly associated with metabolic abnormalities. Traditionally, the pathogenesis of MAFLD has mainly been attributed to genetic susceptibility and unhealthy lifestyles (such as high-calorie diets and sedentary behavior). However, in recent years, environmental factors, especially air pollution, have been confirmed as independent risk factors and important promoting factors for MAFLD development and further disease progression. This review summarizes current epidemiological findings on the link between air pollution exposure and MAFLD, while exploring its potential biological mechanisms involving systemic inflammation, oxidative stress, immune alteration, genetic risk, and epigenetic regulation underlying the relationship between air pollution and hepatic steatosis. It also reviews the additive interaction between air pollution and lifestyle or socioeconomic factors in MAFLD. Finally, we also discuss multilevel strategies spanning individual-, community-, national-, and global-level cooperation to address the increasing public health burden caused by air pollution. Therefore, incorporating the assessment and control of air pollution into the comprehensive strategies for MAFLD prevention and treatment has important scientific value and public health significance. Full article

Obesity and its metabolic complications represent a major global health challenge, and food-derived bioactive peptides are emerging as promising dietary interventions. In this study, two hemp seed protein-derived tetrapeptides with pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory activity, APAM and RLPA, were co-administered with a high-fat diet (HFD) to male C57BL/6J mice at 25 and 100 mg/kg body weight for 10 weeks. Both peptides dose-dependently alleviated HFD-induced body weight gain, visceral fat accumulation, hepatic steatosis, dyslipidemia, hyperglycemia, and systemic inflammation. Mechanistically, both peptides inhibited intestinal PL and CE activities and enhanced fecal lipid excretion, supporting direct suppression of intestinal fat digestion. 16S rRNA gene sequencing revealed partial restoration of HFD-disrupted gut microbiota, with APAM preferentially enriching Bifidobacterium and Roseburia, while RLPA promoted Akkermansia and Lactobacillus, accompanied by differential improvements in fecal short-chain fatty acid (SCFA) profiles. Hepatic transcriptomics identified the PPAR signaling pathway as a shared regulatory hub, and multi-omics integration revealed significant correlations linking gut microbiota, SCFA production, hepatic gene expression, and metabolic phenotypes. These findings suggest a dual-pathway anti-obesity mechanism integrating intestinal lipid digestion inhibition with gut–liver axis modulation, and highlight hemp seed protein-derived peptides as potential functional food ingredients for obesity prevention. Full article

Polycystic ovary syndrome (PCOS) is frequently accompanied by visceral obesity, insulin resistance, low-grade chronic inflammation, and metabolic syndrome (MetS). These alterations promote significant dysfunction in adipose tissue and liver metabolism through cytokine production. Growing evidence indicates that the interaction between hepatokines and adipokines plays a central role in the development of metabolic and hepatic abnormalities in women with PCOS. This narrative review was conducted to analyze the relationship between adipose tissue dysfunction and liver metabolic impairment in women with PCOS, emphasizing the involvement of hepatokines and adipokines in insulin resistance, inflammation, hepatic steatosis, hepatic fibrosis and MetS. From this perspective, contemporary clinical, biochemical, and molecular studies were reviewed to evaluate how adipocyte-derived factors and hepatocyte-derived cytokines influence metabolic homeostasis in the liver and adipose tissue in women with PCOS. Increased visceral adiposity in PCOS enhances the release of free fatty acids (FFAs) to the liver, resulting in hepatotoxicity, oxidative stress, and hepatic inflammation. Several hepatokines, including fetuin-A, angiopoietin-like protein 3 (ANGPTL3), selenoprotein P(Sep-P), and hepassocin (HPS), show abnormal circulating levels in PCOS and are strongly associated with insulin resistance, dyslipidemia, and progression to hepatic steatosis. In contrast, fibroblast growth factor 21 (FGF-21), follistatin, and interleukin (IL-6) may exert dual effects. Adipokines, such as resistin, visfatin, apelin, and retinol-binding protein 4 (RBP-4), contribute to chronic inflammation, impaired glucose metabolism, androgen excess, and hepatic steatosis and fibrosis. Some of these adipokines, such as leptin and vaspin, may exert both beneficial and detrimental effects, while others, including chemerin and omentin, appear to play predominantly beneficial roles in metabolism. Reduced adiponectin-to-leptin levels further aggravate metabolic dysfunction. These changes indicate that adipose tissue–liver crosstalk is a key mechanism linking PCOS and MetS. Overall, metabolic disturbances in PCOS are strongly mediated by dysregulated communication between adipose tissue and the liver. Altered hepatokine and adipokine profiles contribute to insulin resistance, liver dysfunction, hypertension and the development of MetS in women with PCOS. Understanding these intricate interactions may support the early identification of high-risk patients and the development of targeted therapeutic strategies. Full article