Development Of Nonalcoholic Fatty Liver Disease Research Articles

Iron metabolism and ferroptosis in nonalcoholic fatty liver disease: what is our next step?

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with increasing prevalence worldwide. NAFLD could develop from simple hepatic steatosis to nonalcoholic steatohepatitis (NASH), NASH-related fibrosis, cirrhosis, and even hepatocellular carcinoma. However, the mechanism of NAFLD development has not yet been fully defined. Recently, emerging evidence shows that the dysregulated iron metabolism marked by elevated serum ferritin, and ferroptosis are involved in the NAFLD. Understanding iron metabolism and ferroptosis can shed light on the mechanisms of NAFLD development. Here, we summarized studies on iron metabolism and the ferroptosis process involved in NAFLD development to highlight potential medications and therapies for treating NAFLD.

Comorbidity of periodontal diseases and non-alcoholic fatty liver disease

Among dental pathologies, periodontal diseases occupy the 2nd place in prevalence after caries. The prevalence of non-alcoholic fatty liver disease (NAFLD) in the general population in the world reaches 33.0% and is detected in all age categories. The presence of common risk factors suggests an indirect interaction between periodontitis and NAFLD, but the question of the possibility of direct interaction without the participation of “intermediaries” is relevant. The review examines the bidirectional relationship between periodontal pathology and NAFLD. The results of experimental and clinical studies indicate that periodontal bacteria, especially Porphyromonas gingivalis, correlate with the development of NAFLD. P. gingivalis has been detected in the liver, and LPS from this bacterium has been shown to be involved in the progression of NAFLD, suggesting a possible direct role of P. gingivalis in NAFLD. In addition, P. gingivalis causes disruption of the intestinal microbiocenosis, which contributes to the progression of NAFLD. There are two possible routes connecting the oral cavity and the liver - hematogenous and enteral diffusion of hepatotoxic components. The emerging concept of changes in the oral microbiota associated with periodontitis is closely related to the role of the mouth-gut-liver axis in the pathogenesis of NAFLD, based on the close relationship between the gut and liver connected by the enterohepatic circulation.

Circulating Bone morphogenetic protein 9(BMP9) as a new biomarker for noninvasive stratification of nonalcoholic fatty liver disease and metabolic syndrome.

Nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome (MetS). Bone morphogenetic protein 9 (BMP9) is an essential factor in glucose, lipid and energy metabolism. This study aims to investigate whether BMP9 can serve as a serological marker for the severity of NAFLD or MetS. Blood samples, clinical data and FibroTouch test were collected from consecutively recruited 263 individuals in Shanghai East hospital. All the participants were divided into three groups: the healthy controls, nonalcoholic fatty liver (NAFL) group and nonalcoholic steatohepatitis (NASH) at-risk group according to the results of FibroTouch test and liver function. Serum BMP9 levels were measured by enzyme-linked immunosorbent assay. Serum BMP9 levels were positively correlated with transaminase, triglyceride, fasting plasma glucose, glycated hemoglobin (HbA1c) and uric acid while it showed a downward trend as the increasing number of MetS components. Furthermore, it differentiated NASH at-risk (58.13 ± 2.82ng/L) from the other groups: healthy control (70.32 ± 3.70ng/L) and NAFL (64.34 ± 4.76ng/L) (p < 0.0001). Controlled attenuation parameter of liver fat and liver stiffness measurement were negatively correlated with BMP9 levels, while high-density lipoprotein levels were positively correlated. The risk of developing NAFLD increased along with elevated serum BMP9 and BMI, and a significantly higher risk was observed in men compared to women. BMP9 should be considered a protective factor for the onset and development of NAFLD, as well as a promising biomarker for the severity of the NAFLD and MetS.

The Pathophysiological Associations Between Obesity, NAFLD, and Atherosclerotic Cardiovascular Diseases.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.

Relation between Body Composition Trajectories from Childhood to Adolescence and Nonalcoholic Fatty Liver Disease Risk.

NAFLD has become the leading cause of chronic liver disease in children, as a direct consequence of the high prevalence of childhood obesity. This study aimed to characterize body composition trajectories from childhood to adolescence and their association with the risk of developing nonalcoholic fatty liver disease (NAFLD) during adolescence. The participants were part of the 'Chilean Growth and Obesity Cohort Study', comprising 784 children who were followed prospectively from age 3 years. Annual assessments of nutritional status and body composition were conducted, with ultrasound screening for NAFLD during adolescence revealing a 9.8% prevalence. Higher waist circumference measures were associated with NAFLD from age 3 years (p = 0.03), all skin folds from age 4 years (p < 0.01), and DXA body fat measurements from age 12 years (p = 0.01). The fat-free mass index was higher in females (p = 0.006) but not in males (p = 0.211). The second and third tertiles of the fat mass index (FMI) had odds ratios for NAFLD during adolescence of 2.19 (1.48-3.25, 95% CI) and 6.94 (4.79-10.04, 95% CI), respectively. Elevated waist circumference, skin folds, and total body fat were identified as risk factors for future NAFLD development. A higher FMI during childhood was associated with an increased risk of NAFLD during adolescence.

Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH. Dataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined. A total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells. We proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.

Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults

BackgroundThe specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD.MethodsThe data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites.ResultsAmong the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD.ConclusionsWe confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.

Optimizing lifestyle profiles is potential for preventing nonalcoholic fatty liver disease and enhancing its survival

The aim of this study was to evaluate the association between lifestyle profile and disease incidence/mortality in patients with non-alcoholic fatty liver disease (NAFLD). Lifestyle profiles ascertainment was based on the latent profile analysis. The associations of lifestyle profile and outcomes were analyzed by multivariate logistic or Cox regressions. Four lifestyle profiles (profile 1 and 2 for male, profile 3 and 4 for female) were established for all participants. Compared to profile 1, profile 2 (P = 0.042) and profile 3 (P = 0.013) had lower incidence for NAFLD. In contrast, profile 4 showed similar NAFLD prevalence compared to profile 1 (P = 0.756). Individuals with NAFLD within profile 3 had the best long-term survival, and the HR was 0.55 (95% CI 0.40–0.76) for all-cause mortality (compared to profile 1). Profile 4 (P = 0.098) and profile 2 (P = 0.546) had similar all-cause survival compared to profile 1. We explored the associations of healthy lifestyle score with mortality and incidence of NAFLD stratified by lifestyle profiles. We observed that with the increase of healthy lifestyle score, participants within profile 2 did not display lower NAFLD incidence and better long-term survival in NAFLD cases. In this study, lifestyle profiles were constructed in NHANES participants. The distinct lifestyle profiles may help optimize decision-making regarding lifestyle management in preventing NAFLD development, as well as selection of a more personalized approach for improving NAFLD survival.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Isoleucine‐restricted diets improve high‐fat diet‐induced nonalcoholic fatty liver disease via regulating insulin resistance and gut microbiota

AbstractObesity, caused by a long‐term high‐fat diet, is a risk factor for insulin resistance and nonalcoholic fatty liver disease (NAFLD). The gut microbiota plays an important role in NAFLD development by producing lipopolysaccharides (LPS). Isoleucine (ILE), as one of the branched‐chain amino acids (BCAAs), has a negative effect on glucose and lipid metabolism in obese mice. Therefore, we speculated that isoleucine‐restricted diets could prevent high‐fat diet‐induced insulin resistance and NAFLD. For this purpose, 30 C57BL/6J mice received a control check diet (CK), a high‐fat diet (HFD), and a isoleucine‐restricted diet (IR) for 12 weeks, respectively. The current study revealed that IR diets reversed HFD‐induced weight gain, increased fasting glucose levels, and lipid metabolism disorder. Furthermore, IR diets attenuated HFD‐induced hepatic inflammation by regulating the LPS/TLR4/NF‐κB signaling pathway. Moreover, hepatic insulin resistance and gluconeogenesis disorder were significantly improved by IR diets. In addition, IR diets reshaped HFD‐induced gut microbiota imbalance, reflected in decreasing the proportion of Proteobacteria phylum and LPS contents. Taken together, our studies support that restricting isoleucine in high‐fat diets was a novel means of preventing obesity‐induced NAFLD and insulin resistance.

Independent associations of serum calcium with or without albumin adjustment and serum phosphorus with nonalcoholic fatty liver disease: results from NHANES 1999-2018.

The associations of serum calcium and phosphorus with nonalcoholic fatty liver disease (NAFLD) remain unclear. In addition, there may be an effect of albumin correction on the association between serum calcium and NAFLD. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). Eligible adult individuals from NHANES 1999-2018 were recruited for the study. We explored the associations of serum calcium, albumin-adjusted serum calcium, and serum phosphorus with NAFLD in multivariable-adjusted regression models. In addition, restricted cubic spline (RCS), stratified analysis, and multiple sensitivity analyses were used for further elaboration. The study sample consisted of 20,900 participants, with an observed NAFLD prevalence of 44.65%. Fully adjusted models indicated that serum calcium was inversely associated with NAFLD (odds ratio [OR] and 95% confidence interval [CI] = 0.70 (0.62, 0.78), p<0.0001), whereas albumin-adjusted serum calcium was positively associated with NAFLD (OR and 95% CI=1.59 (1.41, 1.79), p<0.0001). RCS modeling indicated that serum calcium without and with albumin adjustment was linearly(p nonlinear = 0.083) and nonlinearly (p nonlinear < 0.0001) associated with NAFLD, respectively, whereas serum phosphorus showed a U-shaped relationship with NAFLD(p nonlinear < 0.0001). Gender is a significant influence in all associations, and other variables may also have an effect. Sensitivity analyses indicated that these associations were independent of additional significant confounders. Serum calcium and phosphorus were significantly associated with the development of NAFLD. These findings suggest the potential clinical significance of serum calcium/phosphorus and albumin levels in individuals at high risk for NAFLD. Our study supports the potential role of serum calcium/phosphorus homeostasis in the pathophysiology of NAFLD and could serve as NAFLD-related biomarkers.

Unveiling global research trends and hotspots on mitochondria in NAFLD from 2000 to 2023: A bibliometric analysis.

Nonalcoholic fatty liver disease (NAFLD) has garnered significant attention in the past decade as a prevalent chronic liver condition. Despite a growing body of evidence implicating mitochondria in NAFLD development, comprehensive bibliometric analyses within this research domain are scarce. This study aims to provide a thorough overview of the knowledge framework and key research areas related to mitochondria in the context of NAFLD, utilizing bibliometric techniques. A comprehensive search of publications on mitochondria in NAFLD from 2000 to 2023 was conducted using the Web of Science Core Collection database. VOSviewers, CiteSpace, and the R package "bibliometrix" were employed for a precise assessment of the literature. Examining 2530 articles from 77 countries, primarily led by the United States and China, revealed a consistent increase in publications on mitochondria's role in NAFLD. Leading research institutions include the University of Coimbra, the University of Missouri, the Chinese Academy of Sciences, Fudan University, and Shanghai Jiao Tong University. Notably, the International Journal of Molecular Sciences emerged as the most popular journal, and Hepatology was the most frequently cited. With contributions from 14,543 authors, Michael Roden published the highest number of papers, and A. J. Samyal was the most frequently cocited author. Key focus areas include investigating mitochondrial mechanisms impacting NAFLD and developing therapeutic strategies targeting mitochondria. Emerging research hotspots are associated with keywords such as "inflammation," "mitochondrial dysfunction," "autophagy," "obesity," and "insulin resistance." This study, the first comprehensive bibliometric analysis, synthesizes research trends and advancements in the role of mitochondria in NAFLD. Insights derived from this analysis illuminate current frontiers and emerging areas of interest, providing a valuable reference for scholars dedicated to mitochondrial studies.

Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

Non-alcoholic fatty liver disease and Helicobacter pylori infection: is there a relationship? Review

The article outlines the relevance of finding a connection between non‑alcoholic fatty liver disease (NAFLD) and Helicobacter pylori infection. The presented data of the majority of studies indicate the presence of Helicobacter pylori infection as a risk factor for the development of NAFLD. In addition, a number of researchers point to the possibility of the influence of Helicobacter pylori on important pathogenetic chains of NAFLD: insulin resistance, the state of the intestinal microbiota, the level of such hormones as ghrelin, leptin, adiponectin, and also that the effect of Helicobacter pylori (H. pylori) toxins can cause direct damage to the liver and that Helicobacter pylori invasion of the small intestine mucosa can increase the permeability of the latter, disrupting the functioning of the gut—liver axis. The article emphasizes the relationship between H. pylori infection and an unfavorable metabolic profile: dyslipidemia, body mass index, blood pressure, fasting blood glucose, and insulin resistance. In addition, research data on the novelty of higher levels of aspartate and alanine aminotransferase in Helicobacter‑positive patients compared to Helicobacter‑negative patients, in the absence of differences in liver fibrosis, are given. Separately, the research data are given, which indicate that the successful eradication of Helicobacter infection does not have a significant effect on liver steatosis, but probably reduces the severity of insulin resistance. Also, the authors draw attention to the fact that in a number of studies, the connection of H. pylori with NAFLD was not found, and no significant differences were found in the levels of high and low‑density lipoprotein cholesterol in people with Helicobacter infection compared to Helicobacter‑negative ones. The authors conclude that today there is no clear understanding of the role of Helicobacter pylori infection in the NAFLD pathogenesis, which requires further research because, after all, most researchers testify in favor of the fact that H. pylori infection can be one of the risk factors, contributing to the emergence and progression of NAFLD, and eradication of H. pylori may be important in the treatment of this disease.

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota.

Gut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD.

Perilipin 5 deletion protects against nonalcoholic fatty liver disease and hepatocellular carcinoma by modulating lipid metabolism and inflammatory responses

The molecular mechanisms underlying the transition from nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC) are incompletely understood. During the development of NAFLD, Perilipin 5 (PLIN5) can regulate lipid metabolism by suppressing lipolysis and preventing lipotoxicity. Other reports suggest that the lack of PLIN5 decreases hepatic injury, indicating a protective role in NAFLD pathology. To better understand the role of PLIN5 in liver disease, we established mouse models of NAFLD and NAFLD-induced HCC, in which wild-type and Plin5 null mice were exposed to a single dose of acetone or 7,12-dimethylbenz[a]anthracene (DMBA) in acetone, followed by a 30-week high-fat diet supplemented with glucose/fructose. In the NAFLD model, RNA-seq revealed significant changes in genes related to lipid metabolism and immune response. At the intermediate level, pathways such as AMP-activated protein kinase (AMPK), signal transducer and activator of transcription 3 (STAT3), c-Jun N-terminal kinase (JNK), and protein kinase B (AKT) were blunted in Plin5-deficient mice (Plin5−/−) compared to wild-type mice (WT). In the NAFLD-HCC model, only WT mice developed liver tumors, while Plin5−/− mice were resistant to tumorigenesis. Furthermore, only 32 differentially expressed genes associated with NALFD progession were identified in Plin5 null mice. The markers of mitochondrial function and immune response, such as the peroxisome proliferator‐activated receptor-γ, coactivator 1‐α (PGC-1α) and phosphorylated STAT3, were decreased. Lipidomic analysis revealed differential levels of some sphingomyelins between WT and Plin5−/− mice. Interestingly, these changes were not detected in the HCC model, indicating a possible shift in the metabolism of sphingomelins during carcinogenesis.

Sex-Specific Association between Sodium Intake Estimated by 24-Hour Urinary Sodium Excretion and Nonalcoholic Fatty Liver Disease: The Community-Based Prospective Cohort Study.

Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40-69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka's equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD.

The Signal Intensity Ratio of Pancreas to Spleen in Magnetic Resonance Imaging Can Predict Nonalcoholic Fatty Liver Disease After Pancreaticoduodenectomy.

Signal intensity ratio of pancreas to spleen (SI ratio p/s ) on fat-suppressed T1-weighted images of magnetic resonance imaging has been associated with pancreatic exocrine function. We here investigated the predictive value of the SI ratio p/s for the development of nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD). This study comprised 208 patients who underwent PD. NAFLD was defined as a liver-to-spleen attenuation ratio of <0.9 calculated by a computed tomography 1 year after surgery. SI ratio p/s was calculated by dividing the average pancreas SI by the spleen SI. We retrospectively investigated the association of clinical variables including the SI ratio p/s and NAFLD by univariate and multivariate analyses. NAFLD after 1 year was developed in 27 patients (13%). In multivariate analysis, the SI ratio p/s < 1 ( P < 0.001) was an independent predictor of incidence of NAFLD. The SI ratio p/s < 1 was associated with low amylase level of the pancreatic juice ( P < 0.001) and progressed pancreatic fibrosis ( P = 0.017). According to the receiver operating characteristics curve, the SI ratio p/s had better prognostic ability of NAFLD than the remnant pancreas volume. The SI ratio p/s is useful to predict NAFLD development after PD. Moreover, the SI ratio p/s can be a surrogate marker, which represents exocrine function of the pancreas.

Association between healthy beverage index and nonalcoholic fatty liver disease in the Ravansar noncommunicable disease cohort study

The quality of drinks affects the functioning of the liver. In recent decades, the variety of high-calorie and sweet drinks has increased. The objective of this study was to explore the association between Healthy Beverage Index (HBI) and the risk of nonalcoholic fatty liver disease (NAFLD) among adults. We included 6,276 participants aged 35 to 65 from the Ravansar Non-Communicable Disease (RaNCD) cohort study at baseline. NAFLD is defined based on the fatty liver index (FLI), calculated using anthropometric measurements and non-invasive markers. The HBI was developed using a combination of water, low-fat milk, 100% fruit juice, sugar-sweetened beverages, met fluid requirement and % energy from beverages. Logistic and linear regression models were employed to investigate the associations of the HBI and high FLI. The average FLI was significantly lower in the first tertile of HBI compared to the third tertile (47.83 vs. 45.77; P = 0.001). After adjusting for confounding variables, the odds of high FLI decreased by 28% (OR 0.72, 95% CI 0.63, 0.82) in the second tertile of HBI and by 21% in the third tertile (OR 0.79, 95% CI 0.70, 0.91). There was no correlation between gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate transaminase (AST) levels with HBI. The study findings indicate an inverse association between high FLI and HBI. Therefore, it is recommended to consume healthy beverages and without added sugar. However, additional longitudinal studies are required to examine the association between beverage consumption and the development of NAFLD.

U-Shaped relationship of insulin-like growth factor I and incidence of nonalcoholic fatty liver in patients with pituitary neuroendocrine tumors: a cohort study.

Although the role of insulin-like growth factor I (IGF-1) in nonalcoholic fatty liver disease (NAFLD) has garnered attention in recent years, few studies have examined both reduced and elevated levels of IGF-1. The aim of this study was to examine the potential relationship between IGF-1 levels and the risk of new-onset NAFLD in patients with pituitary neuroendocrine tumors (PitNET). We employed multivariable Cox regression models and two-piecewise regression models to assess the association between IGF-1 and new-onset NAFLD. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated to quantify this association. Furthermore, a dose-response correlation between lgIGF-1 and the development of NAFLD was plotted. Additionally, we also performed subgroup analysis and a series sensitivity analysis. A total of 3,291 PitNET patients were enrolled in the present study, and the median duration of follow-up was 65 months. Patients with either reduced or elevated levels of IGF-1 at baseline were found to be at a higher risk of NAFLD compared to PitNET patients with normal IGF-1(log-rank test, P < 0.001). In the adjusted Cox regression analysis model (model IV), compared with participants with normal IGF-1, the HRs of those with elevated and reduced IGF-1 were 2.33 (95% CI 1.75, 3.11) and 2.2 (95% CI 1.78, 2.7). Furthermore, in non-adjusted or adjusted models, our study revealed a U-shaped relationship between lgIGF-1 and the risk of NAFLD. Moreover, the results from subgroup and sensitivity analyses were consistent with the main results. There was a U-shaped trend between IGF-1 and new-onset NAFLD in patients with PitNET. Further evaluation of our discoveries is warranted.