Metabolic Dysfunction-associated Fatty Liver Disease Research Articles

Impact of Metabolic Dysfunction-Associated Fatty Liver Disease on the Prognosis of Patients With Hepatocellular Carcinoma After Radical Resection: A Retrospective Study

Impact of Metabolic Dysfunction-Associated Fatty Liver Disease on the Prognosis of Patients With Hepatocellular Carcinoma After Radical Resection: A Retrospective Study

Microbiome and Metabolomics Reveal the Effect of Gut Microbiota on Liver Regeneration of Fatty Liver Disease

Metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with impaired regenerative capacity and poor postoperative prognosis following hepatectomy. Previous research has highlighted the importance of the gut-liver axis in the physiological and pathological processes of the liver. However, the contribution of gut bacteria to the regeneration of livers with MAFLD and its metabolic regulatory mechanisms remain elusive. Partial hepatectomy (PHx) was performed on C57Bl/6J mice fed with high-fat diet (HFD) for 12 weeks. Pathological examination, immunohistochemistry, and qRT-PCR analysis were performed to assess the severity of steatosis and proliferative potential. The gut microbiome was examined by 16S rRNA gene sequencing and shotgun metagenomics, whereas liver metabolomics was analysed via untargeted and targeted metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS). HFD-induced hepatic steatosis in mice led to impaired liver regeneration following PHx. The gut microbiota and liver metabolites were altered along with the liver regeneration process. Longitudinal time-series analysis revealed dynamic alterations in these data, whereas correlation analysis screened out bacterial candidates that potentially influence liver regeneration in MAFLD by modulating metabolic pathways. Among these bacteria, the dominant bacterium Akkermansia was selected for subsequent investigation. MAFLD mice gavaged with Akkermansia muciniphila (A.muciniphila) exhibited reduced liver lipid accumulation and accelerated liver regeneration, possibly through the regulation of the tricarboxylic acid (TCA) cycle. These data demonstrated the interplay between the gut microbiome, liver metabolomics, and liver regeneration in mice with MAFLD. A.muciniphila has the potential to serve as a clinical intervention agent to accelerate postoperative recovery in MAFLD. This work was supported by the Research Project of Jinan Microecological Biomedicine Shandong Laboratory [JNL-2022008B]; the Zhejiang Provincial Natural Science Foundation of China [LZ21H180001]; the Fundamental Research Funds for the Central Universities [No. 2022ZFJH003].

Increased magnesium intake does not mitigate MAFLD risk associated with magnesium deficiency

Serum magnesium cannot accurately assess magnesium deficiency. The association between magnesium deficiency and metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear. Selecting 3,377 participants in the United States, we assessed the degree of magnesium deficiency in the population using magnesium depletion score (MDS). Multinomial logistic regression assessed the association between magnesium deficiency and MAFLD. Subgroup analyses assessed the association between dietary magnesium intake and MAFLD under different magnesium deficiency statuses. Structural equation modeling (SEM) revealed mediation effects. Magnesium deficiency was associated with MAFLD (ORseverevs.none: 1.69, 95%CI: 1.16–2.46; p for trend < 0.001). Magnesium intake was negatively associated with MAFLD only in the subgroup without magnesium deficiency (p for trend < 0.01). Inflammation, oxidative stress, and aging significantly mediated the association between MDS and MAFLD (all p < 0.05). In American adults, magnesium deficiency assessed by MDS might be a risk factor for MAFLD, with inflammation, oxidative stress, and aging potentially being key mechanisms. Simply increasing magnesium intake would not mitigate MAFLD risk associated with magnesium deficiency. Correcting magnesium deficiency might prevent MAFLD.

Elevated thyroid autoantibodies as risk factors for metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus

Elevated thyroid autoantibodies as risk factors for metabolic dysfunction-associated fatty liver disease in type 2 diabetes mellitus

Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association.

Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist's perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.

Aspartate aminotransferase-to-platelet ratio index outperforms Fibrosis-4 in 2843 Korean patients with metabolic dysfunction-associated steatotic liver disease.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD. This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed. Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis≥F3, and 0.890, 0.884, and 0.889 for fibrosis≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis≥F2, 0.788, 0.814, and 0.79 for fibrosis≥F3, and 0.846, 0.859, and 0.856 for fibrosis≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64years for fibrosis≥F4. The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Alterations in Glutathione Redox Homeostasis in Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review

Alterations in Glutathione Redox Homeostasis in Metabolic Dysfunction-Associated Fatty Liver Disease: A Systematic Review

Metabolic Dysfunction Associated Fatty Liver Disease in Long-Term Cholecystectomy Patients: A Cross-Sectional Study.

Cholecystectomy, while generally safe with low perioperative morbidity and mortality, has been linked to an increase in metabolic disorders. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a globally prevalent condition that leads to both hepatic and systemic complications. This study aimed to investigate the association between cholecystectomy and MAFLD. This cross-sectional study was designed to evaluate the relationship between cholecystectomy and MAFLD. Metabolic dysfunction-associated fatty liver disease was defined by the presence of hepatic steatosis in combination with any of the following conditions: diabetes mellitus (fasting plasma glucose ≥126 mg/dL), overweight (body mass index (BMI) ≥25 kg/m2), or metabolic dysregulation. A total of 163 participants with BMI ≥25 kg/m2, including consecutive cholecystectomized (N = 83) and non-cholecystectomized (N = 80) subjects, were included. The prevalence of MAFLD was found in 64 out of 83 (77.1%) cholecystectomized patients and in 30 out of 80 (37.5%) non-cholecystectomized subjects (P < .001). When age, gender, BMI, exercise habits, hypertension, diabetes mellitus, and cholecystectomy status were included in regression analyses, we found that only BMI [odds ratio (OR) = 1.155 (95% CI: 1.040-1.283)] and cholecystectomy [OR = 4.540 (95% CI: 2.200-9.370)] were independently associated with MAFLD (both P < .01). ROC analysis identified 10 years as the cut-off, with MAFLD risk being 2.7-7.3 times higher in patients with cholecystectomy for ≤10 and >10 years. In our study, MAFLD was found to be 4.5 times more likely in cholecystectomized patients compared to those without cholecystectomy, with a significant increase in frequency observed after 10 years. These results suggest that cholecystectomized patients should be monitored for MAFLD.

Decoding the fatty liver-hyperuricemia link in the obese and nonobese hypertensive patients: insights from a cohort study

Metabolic-dysfunction-associated fatty liver disease (MAFLD) and serum uric acid are closely related to cardiovascular and cerebrovascular diseases. However, the causal association between MAFLD and serum uric acid remains unclear. A total of 3417 patients without hyperuricemia were included in the final analysis. MAFLD was defined as fatty liver index (FLI) ≥ 30. Multivariate Cox regression analysis was used to explore the association between FLI and new-onset hyperuricemia. Restricted cubic splines and threshold saturation effect analysis were used to detect nonlinear associations. The mean age was 62.8 ± 8.3 year, and 68.5% were women. A total of 738 (21.6%) hypertensive patients developed new-onset hyperuricemia, 388 (11.4%) new-onset hyperuricemia10 and 190 (5.6%) new-onset hyperuricemia20 during the 4-year midday follow-up period. In the fully adjusted model, compared with the Q1 (FLI ≤ 8.5) group, the risk of hyperuricemia increased by 56% (HR: 1.56; 95% CI: 1.02, 2.38) in the Q4 (FLI > 39.4) group, new-onset hyperuricemia10 increased by 108% (HR: 2.08; 95% CI: 1.15, 3.78), and new-onset hyperuricemia20 increased by 156% (HR: 2.56; 95% CI: 1.11, 5.94), respectively. Saturation effects showed a nonlinear association between FLI and new-onset hyperuricemia (p for log likelihood ratio test < 0.05). Subgroup analysis and stratified analysis showed that there had a significantly higher risk of new-onset hyperuricemia in the patients with normal body mass index (< 24 kg/m2) (p for interaction: 0.018) and non-central obesity (p for interaction: 0.024). MAFLD is an independent risk factor for hyperuricemia in hypertensive patients, especially in patients with normal body mass index and non-central obesity.

Identification of biomarkers for the diagnosis in colorectal polyps and metabolic dysfunction-associated steatohepatitis (MASH) by bioinformatics analysis and machine learning

Colorectal polyps are precursors of colorectal cancer. Metabolic dysfunction associated steatohepatitis (MASH) is one of metabolic dysfunction associated fatty liver disease (MAFLD) phenotypic manifestations. Much evidence has suggested an association between MASH and polyps. This study investigated the biomarkers of MASH and colorectal polyps, and the prediction of targeted drugs using an integrated bioinformatics analysis method. Differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed on GSE89632 and GSE41258 datasets, 49 shared genes revealed after intersection. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses depicted they were mainly enriched in apoptosis, proliferation and infection pathways. Machine learning algorithms identified S100P, FOXO1, and LPAR1 were biomarkers for colorectal polyps and MASH, ROC curve and violin plot showed ideal AUC and stable expression patterns in both the discovery and validation sets. GSEA analysis showed significant enrichment of bile acid and fatty acid pathways when grouped by the expression levels of the three candidate biomarkers. Immune infiltration analysis showed a significant infiltration of M0 macrophages and Treg cells in the colorectal polyps group. A total of 9 small molecule compounds were considered as potential chemoprevention agents in MASH and colorectal polyps by using the CMap website. Using integrated bioinformatics analysis, the molecular mechanism between MASH and colorectal polyps has been further explored.

Protocatechuic acid relieves ferroptosis in hepatic lipotoxicity and steatosis via regulating NRF2 signaling pathway

Ferroptosis represents a newly programmed cell death, and the process is usually accompanied with iron-dependent lipid peroxidation. Importantly, ferroptosis is implicated in a myriad of diseases. Recent literature suggests a potential position of ferroptosis in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD), the most widespread liver ailment worldwide. Intriguingly, several functional genes and metabolic pathways central to ferroptosis are regulated by nuclear factor erythroid-derived 2-like 2 (NRF2). In current work, we aim to identify protocatechuic acid (PCA), a primary metabolite of antioxidant polyphenols, as a potent NRF2 activator and ferroptosis inhibitor in the hepatic lipotoxicity and steatosis models. Herein, both NRF2+/+ and NRF2−/− cell lines and mice were used to analyze the importance of NRF2 in PCA function, and hepatic lipotoxicity and steatosis models were induced by palmitic acid and high-fat diet respectively. Our results indicated that ferroptosis was mitigated by PCA intervention in hepatic cells. Furthermore, PCA exhibited therapeutic efficacy against ferroptosis, as well as hepatic lipotoxicity and steatosis. The protective role of PCA was predominantly mediated through NRF2 activation, potentially elucidating a pivotal mechanism underlying PCA's therapeutic impact on MAFLD. Additionally, the augmented mitochondrial TCA cycle activity observed in hepatic lipotoxicity and steatosis models was ameliorated by PCA, in part via NRF2-dependent pathways, further bolstering PCA's anti-ferroptosis properties. Collectively, our findings underscore PCA’s potential in alleviating hepatic ferroptosis, lipotoxicity and steatosis via inducing activation of NRF2 signaling pathway, offering a promising strategy for the therapy of MAFLD as well as related lipid metabolic disorders.

ASPP2 deficiency promotes the progression of metabolic dysfunction-associated steatohepatitis via ACSL4 upregulation

As a member of the p53-binding protein family, apoptosis-stimulating protein p53 2 (ASPP2) is closely related to autophagy and apoptosis. However, the mechanistic role of ASPP2 in the development of metabolic dysfunction-associated steatohepatitis (MASH) remains elusive. Therefore, we investigated the role and underlying mechanisms of ASPP2 in MASH progression in a mouse model of MASH and a cellular model of metabolic dysfunction-associated fatty liver disease. ASPP2 deficiency significantly promoted the inflammatory response, steatosis, and MASH progression in mice. Through transcriptomic analysis, increased ACSL4 expression was identified as a potential key factor. Further elucidation of the underlying mechanisms demonstrated that ASPP2 deficiency increased lipid accumulation and inhibited mitochondrial respiration capacity in HepG2 cells induced by oleic acid. However, silencing of ACSL4 reversed these effects. Thus, our study indicates that ASPP2 is an important regulator of MASH progression through ACSL4 upregulation, highlighting its potential as an alternative approach to MASH treatment.

Associations of an overall healthy lifestyle with the risk of metabolic dysfunction-associated fatty liver disease

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) affects up to one-third of the global population. Since no approved pharmacotherapy for MAFLD is available, lifestyle modification remains the cornerstone of clinical care. Our study aims to evaluate the association of an overall healthy lifestyle with MAFLD risk.MethodsWe conducted an analysis of 327,387 participants from UK biobank. An overall healthy lifestyle score including six evidence-based lifestyles (diet, alcohol consumption, physical activity, sedentary behavior, sleep, and smoking) was assessed by questionnaires. MAFLD and its subtypes were diagnosed by blood biochemistry, ICD codes, and medication information from touchscreen and verbal interview. The prevalence ratios (PRs) and risk ratios (RRs) were estimated by Poisson regression models with robust variance.ResultsIn the cross-sectional analysis, the PR (95% CI) was 0.83 (0.83 to 0.84) for MAFLD, and 0.83 (0.83 to 0.84) for MAFLD-overweight/obesity (MAFLD-O), 0.68 (0.66 to 0.70) for MAFLD-lean/normal weight and metabolic dysfunction (P-value for heterogeneity < 0.001), and 0.71 (0.71 to 0.72) for MAFLD-type 2 diabetes mellitus (MAFLD-T2D); and 0.68 (0.66 to 0.71) for dual (or more) etiology fatty liver disease (MAFLD-dual) and 0.83 (0.83 to 0.84) for single etiology MAFLD (MAFLD-single) (P-value for heterogeneity < 0.001) for one additional point in the overall healthy lifestyle score. During a median follow-up of 4.4 years, the RR (95% CI) was 0.83 (0.81 to 0.85) for MAFLD, and 0.83 (0.81 to 0.85) for MAFLD-O, 0.71 (0.62 to 0.81) for MAFLD-L, and 0.68 (0.64 to 0.72) for MAFLD-T2D (P-value for heterogeneity < 0.001); and 0.83 (0.81 to 0.85) for MAFLD-dual and 0.70 (0.58 to 0.85) for MAFLD-single (P-value for heterogeneity = 0.08) for one additional point in the overall healthy lifestyle score. These findings were validated in a prospective analysis among 15,721 participants with revisit data, and also supported by fatty liver index and proton density fat fraction data.ConclusionsAn overall healthy lifestyle that includes six evidence-based factors was strongly associated with lower MAFLD risk, especially the subtypes with multiple etiologies.

Dawn of an era of effective treatments for MAFLD

AbstractFatty liver disease is a commonly occurring disease resulting in hepatic and extrahepatic complications. To date, there have been few available treatments beyond conventional lifestyle modification. While lifestyle modifications resulting in weight loss &gt;10% have shown to be beneficial for metabolic dysfunction‐associated steatohepatitis (MASH), for the majority of patients, this is difficult to achieve. The recent approval of resmetirom (a thyroid hormone receptor beta agonist) by the Food and Drug Administration following positive results for histological outcomes in a phase 3 trial has opened the door for new treatments for metabolic (dysfunction)‐associated fatty liver disease (MAFLD) and MASH. There are currently a number of phase 3 trials targeting a variety of signaling pathways involved in the pathogenesis of metabolic steatohepatitis that are also promising. This review focuses on the currently available treatments for MAFLD and MASH, ongoing phase 3 clinical trials, and unresolved controversies in clinical trials in this area.

Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function.

We discuss the article by Koizumi et al published in the World Journal of Gastroenterology. Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease (ALD) and the mechanism of action of elafibranor (EFN), a dual agonist of peroxisome proliferator-activated receptor α (PPARα) and peroxisome PPAR δ (PPARδ). EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis. ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis (ASH), with chronic ASH eventually leading to fibrosis, cirrhosis, and, in some cases, hepatocellular carcinoma. The pathogenesis of ALD is driven by hepatic steatosis, oxidative stress, and acetaldehyde toxicity. Alcohol consumption disrupts lipid metabolism by inactivating PPARα, exacerbating the progression of ALD. EFN primarily activates PPARα, promoting lipolysis and β-oxidation in ethanol-stimulated HepG2 cells, which significantly reduces hepatic steatosis, apoptosis, and fibrosis in an ALD mouse model. Additionally, alcohol disrupts the gut-liver axis at several interconnected levels, contributing to a proinflammatory environment in the liver. EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy, inhibiting apoptosis and inflammatory responses, and enhancing intestinal barrier function through PPARδ activation.

Association between multiple metals exposure and metabolic dysfunction-associated fatty liver disease among Chinese adults

BackgroundPrevious research has investigated the hepatotoxicity of single metal exposure. However, there is limited evidence about metal mixture and their association with metabolic dysfunction-associated fatty liver disease (MAFLD), particularly in the Chinese population. ObjectiveTo investigate the individual and combine effects of 20 metals on MAFLD in a large population in China. MethodsThis study included 3651 participants from the Medical Physical Examination Center of Tongji Hospital, Wuhan, China. MAFLD was identified based on ultrasonic graphic evidence of hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine urinary concentrations of 20 metals. Logistic regression was used to assess the relationship between individual metal and MAFLD, with results presented as odds ratios (ORs) and 95 % confidence intervals (CIs). Weighted quantile sum (WQS) regression was performed to evaluate the combine effect of metals. ResultsThe prevalence of MAFLD among the participants was 32.1 % (1173/3651). In singe-metal analysis, high exposure to zinc (OR =1.42; 95 % CI = 1.27, 1.59) and selenium (OR = 1.23; 95 % CI = 1.10, 1.39) were positively associated with MAFLD. No significant association was found for other metals. WQS regression analysis showed that urinary metal mixture was positively associated with MAFLD (OR = 1.32, 95 % CI: 1.15, 1.51), with zinc (50.4 %) being the largest contributor, followed by barium (10.8 %). ConclusionsIn conclusion, our finding suggested that exposure to the mixture of metals was positively correlated with MAFLD, with zinc being the major contributor.

Associations of Metabolic Dysfunction-Associated Fatty Liver Disease With Peripheral Artery Disease: Prospective Analysis in the UK Biobank and ARIC Study.

There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD. Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk. Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

Efficacy and safety of electroacupuncture for metabolic dysfunction-associated fatty liver disease: a study protocol for a multicentre, randomised, sham acupuncture-controlled, patient-blinded clinical trial

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease in the world and carries an increased risk of liver-related events, but no approved medicine. Electroacupuncture has...

Divergent roles of RIPK3 and MLKL in high-fat diet-induced obesity and MAFLD in mice.

Cell death frequently occurs in the pathogenesis of obesity and metabolic dysfunction-associated fatty liver disease (MAFLD). However, the exact contribution of core cell death machinery to disease manifestations remains ill-defined. Here, we show via the direct comparison of mice genetically deficient in the essential necroptotic regulators, receptor-interacting protein kinase-3 (RIPK3) and mixed lineage kinase domain-like (MLKL), as well as mice lacking apoptotic caspase-8 in myeloid cells combined with RIPK3 loss, that RIPK3/caspase-8 signaling regulates macrophage inflammatory responses and drives adipose tissue inflammation and MAFLD upon high-fat diet feeding. In contrast, MLKL, divergent to RIPK3, contributes to both obesity and MAFLD in a manner largely independent of inflammation. We also uncover that MLKL regulates the expression of molecules involved in lipid uptake, transport, and metabolism, and congruent with this, we discover a shift in the hepatic lipidome upon MLKL deletion. Collectively, these findings highlight MLKL as an attractive therapeutic target to combat the growing obesity pandemic and metabolic disease.

Association of dietary inflammatory index with sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease: a cross-sectional study.

Sarcopenia is a common complication of fatty liver, and sarcopenia increases the risk of advanced liver fibrosis in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD). Chronic inflammation is the crucial link between sarcopenia and fatty liver. An anti-inflammatory diet is expected to be an essential measure to prevent sarcopenia in patients with fatty liver, and the dietary inflammatory index (DII) is a crucial tool for assessing the inflammatory potential of diets. However, the relationship between DII and sarcopenia in patients with fatty liver is unclear. This study investigated the correlation between the dietary inflammatory index (DII) and sarcopenia in patients with Metabolic dysfunction-associated fatty liver disease (MAFLD). Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, with 917 patients with MAFLD participating in the study. Participants were divided into three groups based on DII tertiles: group T1 (n = 305), group T2 (n = 306), and group T3 (n = 306), and binary logistic regression was used to assess the relationship between DII and sarcopenia with stratified analyses based on the weights recommended by the NHANES and multivariate linear regression was used to evaluate the association of DII with total appendicular lean mass. After adjusting for all confounders, DII was significantly and positively associated with the risk of sarcopenia in women [OR: 1.61, 95% CI: (1.226, 2.06), p < 0.001]. The risk of sarcopenia was higher in the T3 group compared to the T1 group [OR: 4.04, 95% CI: (1.66, 9.84), p = 0.002]. DII was negatively associated with appendicular lean mass adjusted for body mass index in both men and women. DII was significantly associated with the risk of sarcopenia in female patients with MAFLD, with higher DII scores related to a higher risk of sarcopenia. Higher DII scores related to a higher risk of sarcopenia in men with significant fibrosis.