This study aimed to explore the association between dietary fiber intake and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), as well as liver fat content, while considering genetic predispositions of MASLD, gut microbial abundance, and butyrate levels. This study analyzed data from 190,276 participants in the UK Biobank. Dietary fiber intake was assessed using 24-h dietary recall. MASLD cases were diagnosed through hospital admission records and death registries, and liver fat content was measured via magnetic resonance imaging. The genetic predispositions of MASLD, gut microbial abundance, and butyrate levels were evaluated using single nucleotide polymorphisms. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). Over a median follow-up of 10.49 years, 1423 MASLD cases were recorded. Elevated dietary fiber intake was associated with a reduced risk of MASLD (HR: 0.72; 95 % CI: 0.58, 0.90) and a lower level of liver fat content (β: -0.97; 95 % CI: -1.21, -0.73) (all P for trend <0.05). Restricted cubic spline analyses further confirmed the linear inverse associations between fiber intake and the risk of MASLD. Notably, the negative associations between dietary fiber intake and both MASLD and liver fat content were consistent across different genetic predispositions of gut microbial abundance and butyrate levels. Moreover, the inverse association between dietary fiber intake and liver fat was strengthened by high genetic susceptibility of MASLD and elevated body mass index (both P for interaction <0.05). Overall, increased dietary fiber consumption was associated with a lower MASLD risk and decreased liver fat content regardless of genetic predispositions of gut microbial abundance and butyrate levels.

In this article, we discuss the recently published article by Soni et al. This study explores the effectiveness of a comprehensive digital health program, RESET care, which integrates personalized dietary plans, structured exercise, and cognitive behavioral therapy delivered through a mobile app equipped with Internet of Things devices such as body composition analyzers and smartwatches. Metabolic dysfunction-associated liver disease (MASLD), a global health burden affecting approximately 25% of the population, demands sustainable lifestyle modifications as its primary management strategy. The study reports that 100% of participants in the comprehensive intervention group (diet + exercise + cognitive behavioral therapy) achieved a weight reduction ≥ 7% (6.99 ± 2.98 kg, 7.00% ± 3.39%; P = 0.002), a clinically significant threshold for MASLD improvement. In addition, participants showed a mean weight reduction of 6.99 kg (101.10 ± 17.85 vs 94.11 ± 17.38, P < 0.001) and a body mass index reduction of 2.18 kg/m² (32.90 ± 3.02 vs 30.72 ± 3.41, P < 0.001). These results underscore the potential of digital health platforms to provide scalable, evidence-based solutions for the treatment of MASLD. While these results highlight the potential of digital platforms in the scalable and personalized management of MASLD, the small study sample size and short duration of follow-up limit the generalizability of the results. Future large-scale, long-term trials are needed to confirm sustained benefits, cost-effectiveness, and broader applicability. This letter contextualizes the study within the evolving landscape of MASLD management and emphasizes the clinical implications of integrating digital technologies into standard care.

Fructose (Fru) consumption has been suggested to contribute to metabolic diseases including metabolic dysfunction-associated steatotic liver disease (MASLD), at least in part, by disturbing intestinal barrier function and intestinal nitric oxide (NO) homeostasis. Honokiol (Hon), a neolignan found in Magnolia officinalis, has been suggested to affect intestinal integrity and barrier function.

We assessed whether Hon affects Fru-induced small intestinal permeability in settings of early MASLD.

Female 8-10-wk-old C57BL/6J mice (n = 7/group) received either a 30% Fru solution + vehicle or plain drinking water + vehicle ± Hon (10 mg/kg bw/d) for 4 wk. Liver damage [e.g. nonalcoholic fatty liver disease activity score (NAS), number of neutrophils, interleukin-6 (IL-6) protein concentration], markers of intestinal permeability (bacterial endotoxin, tight junction proteins), and NO homeostasis in the small intestine were determined in vivo as well as ex vivo in an everted sac model and in Caco-2 cells. One-way and 2-way analysis of variance were performed, respectively.

Hon diminished the development of MASLD, which was associated with a significant lower NAS (-38%), number of neutrophils (-48%), and IL-6 protein concentrations (-38%) in livers of Fru-fed mice. Hon also attenuated Fru-induced alterations of markers of intestinal barrier function with Fru+Hon-fed mice showing lower bacterial toxin levels in portal plasma (-29%, P = 0.075), higher tight junction protein concentrations (+2.4-fold, P < 0.05), and lower NOx concentration (-44%, P < 0.05) as well as NO synthase activity (-35%) in the small intestine compared with Fru+vehicle-fed mice. Moreover, the decrease in AMP-activated protein kinase phosphorylation found in the small intestine of Fru-fed mice was significantly attenuated (+5.3-fold) by the concomitant treatment with Hon in Fru-fed mice. In support of the in vivo findings, Hon significantly attenuated Fru-induced intestinal permeability ex vivo and in Caco-2 cells.

Our data suggest that Hon diminished the development of Fru-induced early MASLD by alleviating impairments in intestinal barrier function.

Chronic liver disease is defined by persistent harm to the liver that might result in decreased liver function. The two prevalent chronic liver diseases are alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). There is ample evidence that the pathogenesis of these two chronic liver diseases is closely linked to gastrointestinal dysfunctions that alters the gut-liver crosstalk. These alterations are mediated through the imbalances in the gut microbiota composition/function that combined with disruption in the gut barrier integrity allows for harmful gut microbes and their toxins to enter the portal circulation and reach the liver to elicit an inflammatory response. This leads to further recruitment of systemic inflammatory cells, such as neutrophils, T-cells, and monocytes into the liver, which perpetuate additional inflammation and the development of progressive liver damage. Many therapeutic modalities, currently used to prevent, attenuate, or treat chronic liver diseases are aimed at modulating gut dysbiosis and improving intestinal barrier function. Betaine is a choline-derived metabolite and a methyl group donor with antioxidant, anti-inflammatory and osmoprotectant properties. Studies have shown that low betaine levels are associated with higher levels of organ damage. There have been several publications demonstrating the role of betaine supplementation in preventing the development of ALD and MASLD. This review explores the protective effects of betaine through its role as a methyl donor and its capacity to regulate the protective gut microbiota and maintain intestinal barrier integrity to prevent the development of these chronic liver diseases. Further studies are needed to enhance our understanding of its therapeutic potential that could pave the way for targeted interventions in the management of not only chronic liver diseases, but other inflammatory bowel diseases or systemic inflammatory conditions.

Pakistan has the third-highest rate of type 2 diabetes globally, following China and India, making this a significant public health crisis. Despite the severity of the issue, efforts from health and policy practitioners to address it remain limited. With millions already diagnosed as pre-diabetic, the rising incidence of diabetes is rapidly becoming a public health emergency that demands immediate attention. This policy brief provides an accessible overview of diabetes, focusing on its types, mechanisms, and preventive measures. It also identifies key contributing factors, such as dietary habits, obesity, physical inactivity, and the influence of modern dietary trends, while proposing strategies for individuals, communities, and policymakers to combat this growing epidemic in Pakistan. The brief emphasizes the need for a multi-level approach that includes public awareness, education, behavioral and dietary changes, and policy interventions to reverse the trend. Strategies discussed include promoting healthy eating, increasing physical activity, managing obesity, and enhancing access to affordable, healthy food. Additionally, the brief highlights the importance of community and government support, such as public health campaigns, infrastructure improvements, and legislative efforts. By adopting this comprehensive approach, Pakistan can take meaningful steps to address the diabetes epidemic and improve public health outcomes.

To examine the relationship between early childhood adiposity, adolescent lifestyles, gut microbiota and steatotic liver disease (SLD) development in adolescents using data from a prospective, longitudinal cohort study.

We included 69 adolescents (14-17 years old) with SLD and 69 adolescents without SLD, matched for BMI-z scores, sex, and age, from the 13-year longitudinal cohort the "Growth and Obesity Cohort Study". Anthropometric data between the ages of 4 and 17 and lifestyle parameters (including diet and physical activity) at 14-17 years old were evaluated. Fecal samples were collected and microbiome composition and function were assessed using 16S ribosomal RNA amplicon sequencing.

Principal component analysis demonstrated dietary intake factors and childhood adiposity factors expanding the distribution variation between case and control groups, respectively. Lower odds of developing SLD during adolescence was associated with higher levels of daily fiber intake during adolescence (adjusted odds ratio = 0.91) and lower childhood adiposity (triceps skinfold at 5 years of age, suprailiac skinfold at 8 and 11 years of age, and waist-to-hip ratio at age 5-9 years). SLD was associated with a lower abundance of specific microbial species, such as Bacteroides vulgatus, which was higher in the control group compared to the case group (control/case abundance ratio = 18.71). B. vulgatus abundance also positively correlated with dietary fiber intake and inversely correlated with childhood adiposity.

Adiposity in early childhood and a low dietary fiber intake may contribute to the pathogenesis of SLD during adolescence, possibly through alterations to the intestinal microbiome; these findings could inform early disease markers and targets for intervention.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with advanced fibrosis increasing mortality risks. Despite the abundance of dietary guidelines for managing NAFLD, the precise impact of diet quality on mortality among individuals with advanced fibrosis remains elusive. This study aims to explore the influence of five dietary quality indexes on mortality among NAFLD patients and advanced fibrosis patients.

This study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 to assess dietary quality based on the Alternate Mediterranean Diet (aMED), Healthy Eating Index-2020 (HEI-2020), Dietary Approach to Stop Hypertension (DASH), Alternate Healthy Eating Index (AHEI), and Dietary Inflammatory Index (DII). Weighted Cox proportional hazard regression models along with restricted cubic splines and subgroup analyses were employed in this study.

The analysis encompassed 3,634 NAFLD patients. After a median follow-up of 89 months, it was found that higher scores on the aMED (HR 0.814, 95% CI 0.681-0.972), HEI-2020 (HR 0.984, 95% CI 0.972-0.997), DASH (HR 0.930, 95% CI 0.883-0.979), and AHEI (HR 0.980, 95% CI 0.966-0.995) were associated with lower mortality risks, while DII scores (HR 1.280, 95% CI 1.098-1.493) indicated an increased risk of mortality. Additionally, a nonlinear relationship was identified solely between AHEI scores and all-cause mortality in NAFLD patients. Notably, among patients with advanced fibrosis, HEI-2020 as a categorical variable (T3: HR 0.519, 95% CI 0.280-0.964), DASH as a continuous variable (continuous: HR 0.921, 95% CI 0.849-0.999), AHEI (continuous: HR 0.971, 95% CI 0.945-0.997; T2: HR 0.545, 95% CI 0.310-0.960; T3: HR 0.444, 95% CI 0.245-0.804), and DII (continuous: HR 1.311, 95% CI 1.121-1.534; T3: HR 2.772, 95% CI 1.477-5.202) exhibited significant associations with all-cause mortality. Subgroup analyses revealed an interaction between AHEI scores and sex among NAFLD patients, where higher AHEI scores correlated with lower all-cause mortality in females, but no such association was observed in males. For other dietary quality, subgroup analyses indicated that their relationships with mortality were robust.

Our study suggests that a high-quality diet could potentially mitigate mortality risk in both NAFLD and advanced fibrosis patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and affects nearly 30% of the adult population and 10% of the pediatric population. It is estimated that this number will double by 2030. MASLD is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver transplantation, as well as a significant risk factor for cardiovascular disease and mortality. Due to the ever-increasing number of patients, the long-term asymptomatic course of the disease, serious complications, and lack of preventive programs, as well as insufficient awareness of the disease among patients and doctors themselves, MASLD is a growing interdisciplinary problem and a real challenge for modern medicine. The main cause of MASLD is an inappropriate lifestyle-inadequate nutrition and insufficient physical activity, which lead to various components of metabolic syndrome. Lifestyle changes-appropriate diet, weight reduction, and systematic physical activity-are also the basis for the prevention and treatment of MASLD. Hence, in recent years, so much importance has been attached to lifestyle medicine, to non-pharmacological treatment as prevention of lifestyle diseases. The narrative review presents possible therapeutic options for non-pharmacological management in the prevention and treatment of MASLD. The best documented and available diets used in MASLD were discussed, focusing on the benefits and drawbacks of the Mediterranean, high-protein, ketogenic, and intermittent fasting diets. In addition, the most recent recommendations regarding physical activity are summarized.

The excessive accumulation of intrahepatic triglyceride (IHTG) in the liver is a risk factor for metabolic diseases, including type 2 diabetes and cardiovascular disease. IHTG can excessively accumulate owing to imbalances in the delivery, synthesis, storage and disposal of fat to, in and from the liver. Although obesity is strongly associated with IHTG accumulation, emerging evidence suggests that the composition of dietary fat, in addition to its quantity, plays a role in mediating IHTG accumulation. Evidence from human cross-sectional and interventional studies indicates that diets enriched with saturated fat compared to other fat types and carbohydrates produce divergent effects on IHTG content. However, the mechanistic reasons for these observations remain unknown. Given the challenges of investigating such mechanisms in humans, cellular models are needed that can recapitulate human hepatocyte fatty acid metabolism. Here, we review what is known from human studies about how dietary fat, its quantity and composition contribute to IHTG accumulation. We also explore the effects of fatty acid composition on hepatocellular fat metabolism from data generated in cellular models to help explain the divergences observed in in vivo studies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently.

Cirrhosis, which represents the end stage of liver fibrosis, remains a life-threatening condition without effective treatment. Therefore, prevention of the progression of liver fibrosis through lifestyle habits such as diet and exercise is crucial. The functional food AHCC, a standardized extract of cultured Lentinula edodes mycelia produced by Amino Up Co., Ltd. (Sapporo, Japan)] has been reported to be effective in improving the pathophysiology of various liver diseases. In this study, the aim was to analyze the influence of AHCC on hepatic stellate cells, which are responsible for liver fibrosis. Eight-week-old male C57BL6/j mice were induced with liver fibrosis by intraperitoneal injection of carbon tetrachloride. Simultaneously, they were orally administered 3% AHCC to investigate its impact on the progression of liver fibrosis. Using the human hepatic stellate cell (HHSteC) line, we analyzed the influence of AHCC on the expression of molecules related to hepatic stellate cell activation. The administration of AHCC resulted in reduced expression of collagen1a, α smooth muscle actin (αSMA), and heat shock protein 47 in the liver. Furthermore, the expression of cytoglobin, a marker for quiescent hepatic stellate cells, was enhanced. In vitro study, it was confirmed that AHCC inhibited αSMA by inducing cytoglobin via upregulating the stress-activated protein kinase/Jun NH2-terminal kinase (SAPK/JNK) pathway through Toll-like receptor (TLR) 2. In addition, AHCC suppressed collagen1a production by hepatic stellate cells through TLR4-NF-κβ pathway. AHCC was suggested to suppress hepatic fibrosis by inhibition of hepatic stellate cells activation. Daily intake of AHCC from mild fibrotic stages may have the potential to prevent the progression of liver fibrosis.NEW & NOTEWORTHY AHCC, a standardized extract of cultured Lentinula edodes mycelia, suppresses liver fibrosis progression by induction of cytoglobin via the Toll-like receptor 2 (TLR2)-stress-activated protein kinase/Jun NH2-terminal kinase (SAPK/JNK) pathway and the inhibition of collagen production via the TLR4-NFκβ pathway in hepatic stellate cells. Daily oral administration of AHCC from the stage of MASLD may have the potential to prevent disease progression to MASH with fibrosis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing in prevalence, impacting over a third of the global population. The advanced form of MASLD, Metabolic dysfunction-associated steatohepatitis (MASH), is on track to become the number one indication for liver transplant. FDA-approved pharmacological agents are limited for MASH, despite over 400 ongoing clinical trials, with only a single drug (resmetirom) currently on the market. This is likely due to the heterogeneous nature of disease pathophysiology, which involves interactions between highly individualized genetic and environmental factors. To apply precision medicine approaches that overcome interpersonal variability, in-depth insights into interactions between genetics, nutrition, and the gut microbiome are needed, given that each have emerged as dynamic contributors to MASLD and MASH pathogenesis. Here, we discuss the associations and molecular underpinnings of several of these factors individually and outline their interactions in the context of both patient-based studies and preclinical animal model systems. Finally, we highlight gaps in knowledge that will require further investigation to aid in successfully implementing precision medicine to prevent and alleviate MASLD and MASH.

Dietary fatty acids (FA) affect metabolic risk factors. The aim of this study was to explore if changes in dietary fat intake during energy restriction were associated with plasma FA composition. The study also investigated if these changes were associated with changes in liver fat, liver stiffness and plasma lipids among persons with non-alcoholic fatty liver disease. Dietary and plasma FA were investigated in patients with non-alcoholic fatty liver disease (n 48) previously enrolled in a 12-week-long open-label randomised controlled trial comparing two energy-restricted diets: a low-carbohydrate high-fat diet and intermittent fasting diet (5:2), to a control group. Self-reported 3 d food diaries were used for FA intake, and plasma FA composition was analysed using GC. Liver fat content and stiffness were measured by MRI and transient elastography. Changes in intake of total FA (r 0·41; P = 0·005), SFA (r 0·38; P = 0·011) and MUFA (r 0·42; P = 0·004) were associated with changes in liver stiffness. Changes in plasma SFA (r 0·32; P = 0·032) and C16 : 1n-7 (r 0·33; P = 0·028) were positively associated with changes in liver fat, while total n-6 PUFA (r -0·33; P = 0·028) and C20 : 4n-6 (r -0·42; P = 0·005) were inversely associated. Changes in dietary SFA, MUFA, cholesterol and C20:4 were positively associated with plasma total cholesterol and LDL-cholesterol. Modifying the composition of dietary fats during dietary interventions causes changes in the plasma FA profile in patients with non-alcoholic fatty liver disease. These changes are associated with changes in liver fat, stiffness, plasma cholesterol and TAG. Replacing SFA with PUFA may improve metabolic parameters in non-alcoholic fatty liver disease patients during weight loss treatment.

(1) Background: Bariatric surgery has demonstrated the capacity to improve metabolic-associated fatty liver disease (MAFLD) in patients with morbid obesity. In addition, the Mediterranean diet contains anti-inflammatory, anti-oxidative, and anti-fibrotic components, promoting a beneficial effect on MAFLD. This study aimed to assess the improvement of MAFLD, specifically liver steatosis, in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGB) and following a hypocaloric Mediterranean-like diet. (2) Methods: A prospective observational pilot study of 20 patients undergoing RYGB was conducted. The participants underwent a magnetic resonance spectroscopy study 2 weeks before the surgical act and one year postoperatively to assess the percentage of lipid content (PLC). The adherence to the Mediterranean diet was determined by the KIDMED test 1 year after surgery. (3) Results: Mean baseline PLC was 14.2 ± 9.4%, and one year after surgery, it decreased to 4.0 ± 1.8% (p < 0.001). A total of 12 patients (60%) were within the range of moderate adherence to the Mediterranean diet, whereas 8 patients (40%) showed a high adherence. The patients with high adherence to the Mediterranean diet presented significantly lower values of postoperative PLC. (4) Conclusions: Liver steatosis significantly reduces after RYGB. This reduction is further improved when associated with a high adherence to a Mediterranean diet.

Several bibliometric analyses have been carried out to identify research hotspots and trends in nonalcoholic fatty liver disease (NAFLD) research. Nonetheless, there are still significant knowledge gaps that must be filled to advance our understanding of and ability to treat NAFLD.

To evaluate, through bibliometric and visual analysis, the current status of related research, related research frontiers, and the developmental trends in the field of diet and NAFLD.

We retrieved publications about diet and NAFLD published between 1987 and 2022 from Scopus. Next, we used VOSviewer 1.6.20 to perform bibliometric analysis and visualization.

We found a total of 1905 studies, including 1637 (85.93%) original articles and 195 (10.24%) reviews, focused on the examination of NAFLD and its correlation with diet that were published between 1987 and 2022. Among the remaining five types of documents, 38 were letters, notes, editorials, meeting minutes, or brief surveys, representing 1.99% of the total documents. The countries with the most publications on this topic were China (n = 539; 28.29%), followed by the United States (n = 379; 19.90%), Japan (n = 133; 6.98%), and South Korea (n = 127; 6.6%). According to the citation analysis, the retrieved papers were cited an average of 32.3 times and had an h-index of 106, with 61014 total citations. The two main clusters on the map included those related to: (1) Inflammation and oxidative stress; and (2) Dietary interventions for NAFLD.

This was the first study to use data taken from Scopus to visualize network mapping in a novel bibliometric analysis of studies focused on diet and NAFLD. After 2017, the two domains that received the most attention were "dietary interventions for NAFL"' and "'inflammation and oxidative stress implicated in NAFLD and its correlation with diet." We believe that this study provides important information for academics, dietitians, and doctors, and that additional research on dietary interventions and NAFLD is warranted.

Nonalcoholic fatty liver disease (NAFLD) is a liver condition that is prevalent worldwide and associated with significant health risks and economic burdens. As it has been linked to insulin resistance (IR), this study aimed to perform a bibliometric analysis and visually represent the scientific literature on IR and NAFLD.

To map the research landscape to underscore critical areas of focus, influential studies, and future directions of NAFLD and IR.

This study conducted a bibliometric analysis of the literature on IR and NAFLD indexed in the SciVerse Scopus database from 1999 to 2022. The search strategy used terms from the literature and medical subject headings, focusing on terms related to IR and NAFLD. VOSviewer software was used to visualize research trends, collaborations, and key thematic areas. The analysis examined publication type, annual research output, contributing countries and institutions, funding agencies, journal impact factors, citation patterns, and highly cited references.

This analysis identified 23124 documents on NAFLD, revealing a significant increase in the number of publications between 1999 and 2022. The search retrieved 715 papers on IR and NAFLD, including 573 (80.14%) articles and 88 (12.31%) reviews. The most productive countries were China (n = 134; 18.74%), the United States (n = 122; 17.06%), Italy (n = 97; 13.57%), and Japan (n = 41; 5.73%). The leading institutions included the Università degli Studi di Torino, Italy (n = 29; 4.06%), and the Consiglio Nazionale delle Ricerche, Italy (n = 19; 2.66%). The top funding agencies were the National Institute of Diabetes and Digestive and Kidney Diseases in the United States (n = 48; 6.71%), and the National Natural Science Foundation of China (n = 37; 5.17%). The most active journals in this field were Hepatology (27 publications), the Journal of Hepatology (17 publications), and the Journal of Clinical Endocrinology and Metabolism (13 publications). The main research hotspots were "therapeutic approaches for IR and NAFLD" and "inflammatory and high-fat diet impacts on NAFLD".

This is the first bibliometric analysis to examine the relationship between IR and NAFLD. In response to the escalating global health challenge of NAFLD, this research highlights an urgent need for a better understanding of this condition and for the development of intervention strategies. Policymakers need to prioritize and address the increasing prevalence of NAFLD.

Non-alcoholic fatty liver disease (NAFLD), characterized by hepatic fat accumulation in individuals consuming little or no alcohol, has become highly prevalent globally. Oxidative stress plays a central role in instigating inflammation and cell death pathways driving NAFLD progression. This case-control study aimed to elucidate the association between circulating levels of the pivotal non-enzymatic antioxidants - coenzyme Q10 and vitamins E and C - and liver injury parameters among 60 Iraqi NAFLD patients versus 30 healthy controls. NAFLD diagnosis entailed over 5% hepatic steatosis on ultrasound excluding other etiologies. Patients spanned three age groups: 20-29, 30-39, and 40-49. Substantially diminished antioxidant levels concurrent with elevated alkaline phosphatase enzyme were unveiled in NAFLD patients relative to controls (all p < 0.001). Age-based analysis reinforced widespread antioxidant depletion and liver enzyme augmentation across NAFLD patients. Significant correlations also emerged between antioxidants and liver parameters. Our novel observations confirm an antioxidant inadequacy likely perpetuating pathogenic oxidative reactions in NAFLD. Restoring such deficits through lifestyle or therapeutic interventions may confer preventative and disease-modifying value.

Susceptibility to metabolic syndrome (MetS) is dependent on genetics, environment, and gene-by-environment interactions, rendering the study of underlying mechanisms challenging. The majority of experiments in model organisms do not incorporate genetic variation and lack specific evaluation criteria for MetS. Here, we derived a continuous metric, the metabolic health score (MHS), based on standard clinical parameters and defined its molecular signatures in the liver and circulation. In human UK Biobank, the MHS associated with MetS status and was predictive of future disease incidence, even in individuals without MetS. Using quantitative trait locus analyses in mice, we found two MHS-associated genetic loci and replicated them in unrelated mouse populations. Through a prioritization scheme in mice and human genetic data, we identified TNKS and MCPH1 as candidates mediating differences in the MHS. Our findings provide insights into the molecular mechanisms sustaining metabolic health across species and uncover likely regulators. A record of this paper's transparent peer review process is included in the supplemental information.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is significant, impacting almost one-third of the global population. MAFLD constitutes a primary cause of end-stage liver disease, liver cancer and the need for liver transplantation. Moreover, it has a strong association with increased mortality rates due to various extrahepatic complications, notably cardiometabolic diseases. While MAFLD is typically correlated with obesity, not all individuals with obesity develop the disease and a significant percentage of MAFLD occurs in patients without obesity, termed lean MAFLD. The clinical features, progression and underlying physiological mechanisms of patients with lean MAFLD remain inadequately characterized. The present review aims to provide a comprehensive summary of current knowledge on lean MAFLD and offer a perspective on defining MAFLD in individuals with normal weight. Key to this process is the concept of metabolic health and flexibility, which links states of dysmetabolism to the development of lean MAFLD. This perspective offers a more nuanced understanding of MAFLD and its underlying mechanisms and highlights the importance of considering the broader metabolic context in which the disease occurs. It also bridges the knowledge gap and offers insights that can inform clinical practice.

Our objective was to measure and compare the intake of macro and micronutrients in a cohort of individuals with Metabolic Syndrome Associated Steatotic Liver Disease (MASLD) compared with matched controls to identify areas of further research in this area; we identified nutrition-associated associations with MASLD in the United States general population.

We used the 2017 - 2018 NHANES dataset. Elastography Controlled Attenuation Parameter (CAP score>280) in the absence of other liver disease was defined as MASLD in adults (>18). Advanced fibrosis was defined by transient elastography >10 kPa. Controls were adults without liver disease.

1648 MASLD cases (11.4 % advanced fibrosis) and 2527 controls were identified. MASLD cases were older (P<0.001), more likely males (P = 0.01), less likely to have a college education (P = 0.04) and more likely married (P = 0.002). MASLD cases were more likely to be of Mexican American or Hispanic ethnicity (P = 0.002), have higher BMI, and have higher prevalence of diabetes, hyperlipidemia and hypertension (P<0.001 for all). MASLD cases had higher hs-CRP (P = 0.02) and ferritin (P = 0.02). MASLD cases had lower total (P = 0.004) and added vitamin E in their diet (P = 0.002), lower vitamin K intake (P = 0.005), and higher selenium intake (P = 0.03). Caloric intake (P = 0.04), carbohydrate intake (P = 0.02), cholesterol intake (P = 0.03) and saturated fatty acid intake (P = 0.05) were higher in MASLD. Individuals with MASLD were more likely to be on a diet (P<0.001), sedentary (P = 0.008) and less likely to participate in moderate or vigorous recreational activities (P<0.001).

The deficiencies of micronutrients and excess of macronutrients point to oxidative stress, pro-inflammatory state, and lipotoxicity as pathways linking the US diet to MASLD. MASLD patients are more often on special diets, which may reflect prior provider counseling on diet changes to improve health.

Cholesterol is an essential lipid molecule in mammalian cells. It is not only involved in the formation of cell membranes but also serves as a raw material for the synthesis of bile acids, vitamin D, and steroid hormones. Additionally, it acts as a covalent modifier of proteins and plays a crucial role in numerous life processes. Generally, the metabolic processes of cholesterol absorption, synthesis, conversion, and efflux are strictly regulated. Excessive accumulation of cholesterol in the body is a risk factor for metabolic diseases such as cardiovascular disease, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). In this review, we first provide an overview of the discovery of cholesterol and the fundamental process of cholesterol metabolism. We then summarize the relationship between dietary cholesterol intake and the risk of developing MASLD, and also the animal models of MASLD specifically established with a cholesterol-containing diet. In the end, the role of cholesterol-induced inflammation in the initiation and development of MASLD is discussed.

Dietary guidelines recommend limiting red meat intake because it has been amply associated with increased cancer mortality, particularly in patients with liver conditions, such as metabolic dysfunction-associated fatty liver disease (MASLD). MASLD is the leading cause of liver dysfunction in the world today, and no specific treatment other than lifestyle correction has yet been established. The aim of this study was to explore the protective role of leafy vegetables when associated with high red meat consumption.

The study cohort included 1646 participants assessed during the fourth recall of the MICOL study, subdivided into two groups based on red meat intake (≤50 g/die vs. >50 g/die), in order to conduct a cancer mortality analysis. The prevalence of subjects that consumed >50 g/die was only 15.73%. Leafy vegetable intake was categorized based on median g/die consumption, and it was combined with red meat intake.

This is the first study to demonstrate that the consumption of about 30 g/die of leafy vegetables reduces the risk of mortality. A strong association with mortality was observed in subjects with MASLD, and the protective role of vegetables was demonstrated.

Steatotic liver disease (SLD) is defined as a fat accumulation in more than 5% of hepatocytes; it can progress to non-alcoholic steatohepatitis (NASH), associated with an increased state of inflammation. The aim of this study was to explore the protective effects of eating eggs and any association with SLD and hypertension (HTN).

The study cohort included 908 participants assessed in the fourth recall of the MICOL study, grouped into four groups, based on NALFD and/or HTN.

The prevalence of HTN and SLD among participants was 31.61%. Overall, the results indicated a statistical significance of egg consumption, showing a protective role against the two disease conditions, in both the raw and adjusted models (RRR = 0.34, p = 0.009, 0.15 to 0.76 95% C.I.).

Many differences were found among the groups, and the protective role of eating eggs was amply demonstrated. We can conclude that it is unwise to demonize the intake of this food and its nutritional properties, in contrast with previous reports in the literature.

The GG genotype of the Patatin-like phosphatase domain-containing 3 (PNPLA3), dietary fat, short-chain fatty acids (SCFA) and branched-chain amino acids (BCAA) are linked with non-alcoholic fatty liver disease. We studied the impact of the quality of dietary fat on plasma (p) and fecal (f) SCFA and p-BCAA in men homozygous for the PNPLA3 rs738409 variant (I148M). Eighty-eight randomly assigned men (age 67.8 ± 4.3 years, body mass index 27.1 ± 2.5 kg/m2) participated in a 12-week diet intervention. The recommended diet (RD) group followed the National and Nordic nutrition recommendations for fat intake. The average diet (AD) group followed the average fat intake in Finland. The intervention resulted in a decrease in total p-SCFAs and iso-butyric acid in the RD group (p = 0.041 and p = 0.002). Valeric acid (p-VA) increased in participants with the GG genotype regardless of the diet (RD, 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.005 and AD, 3.8 ± 0.3 to 9.7 ± 8.5 µmol/g, p = 0.015). Also, genotype relation to p-VA was seen statistically significantly in the RD group (CC: 3.7 ± 0.4 to 4.2 ± 1.7 µmol/g and GG: 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.0026 for time and p = 0.004 for time and genotype). P-VA, unlike any other SCFA, correlated positively with plasma gamma-glutamyl transferase (r = 0.240, p = 0.025). Total p-BCAAs concentration changed in the AD group comparing PNPLA3 CC and GG genotypes (CC: 612 ± 184 to 532 ± 149 µmol/g and GG: 587 ± 182 to 590 ± 130 µmol/g, p = 0.015 for time). Valine decreased in the RD group (p = 0.009), and leucine decreased in the AD group (p = 0.043). RD decreased total fecal SCFA, acetic acid (f-AA), and butyric acid (f-BA) in those with CC genotype (p = 0.006, 0.013 and 0.005, respectively). Our results suggest that the PNPLA3 genotype modifies the effect of dietary fat modification for p-VA, total f-SCFA, f-AA and f-BA, and total p-BCAA.

Cardiometabolic disease (CMD), which encompasses metabolic-associated fatty liver disease (MAFLD), chronic kidney disease (CKD) and cardiovascular disease (CVD), has been increasing considerably in the past 50 years. CMD is a complex disease that can be influenced by genetics and environmental factors such as diet. With the increased reliance on processed foods containing saturated fats, fructose and cholesterol, a mechanistic understanding of how these molecules cause metabolic disease is required. A major pathway by which excessive nutrients contribute to CMD is through oxidative stress. In this review, we discuss how oxidative stress can drive CMD and the role of aberrant nutrient metabolism and genetic risk factors and how they potentially interact to promote progression of MAFLD, CVD and CKD. This review will focus on genetic mutations that are known to alter nutrient metabolism. We discuss the major genetic risk factors for MAFLD, which include Patatin-like phospholipase domain-containing protein 3 (PNPLA3), Membrane Bound O-Acyltransferase Domain Containing 7 (MBOAT7) and Transmembrane 6 Superfamily Member 2 (TM6SF2). In addition, mutations that prevent nutrient uptake cause hypercholesterolemia that contributes to CVD. We also discuss the mechanisms by which MAFLD, CKD and CVD are mutually associated with one another. In addition, some of the genetic risk factors which are associated with MAFLD and CVD are also associated with CKD, while some genetic risk factors seem to dissociate one disease from the other. Through a better understanding of the causative effect of genetic mutations in CMD and how aberrant nutrient metabolism intersects with our genetics, novel therapies and precision approaches can be developed for treating CMD.

There are only limited studies investigating the impact of dietary quality indicators, such as dietary quality index (DQI), dietary diversity score (DDS), and alternative healthy eating index (AHEI), on metabolic dysfunction-associated fatty liver disease (MASLD). Furthermore, these indicators may have different components that could lead to varying results. Therefore, this study aims to assess the nutritional quality indicators and their potential association with MASLD.

The study included 128 recently diagnosed MASLD patients and 256 controls aged between 20 and 60 years. The dietary intake of participants was evaluated using a validated semi-quantitative food frequency questionnaire that consisted of 168 items. In this study, the method used to evaluate dietary diversity was based on five main food groups, specifically bread and grains, vegetables, fruits, meat, and dairy. The AHEI-2010 was computed using data collected from the FFQ.

After adjusting for confounders in the fully adjusted model, a significant negative correlation was observed between DDS and the risk of MASLD (OR 0.41, 95% CI 0.20, 0.97). Participants in the top quartile of AHEI had a 76% lower risk of MASLD compared with those in the bottom quartile after controlling for all potential confounders in the fully adjusted model (OR 0.24, 95% CI 0.12, 0.56).

The results of our study suggest that there is a significant association between adherence to a high-diversity diet and a reduced likelihood of developing MASLD. Similarly, we observed a similar association between adherence to the AHEI diet and a lower risk of MASLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms.

High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms.

Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy.

These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is associated with abnormalities of liver lipid metabolism. On the contrary, a diet enriched with n-3 polyunsaturated fatty acids (n-3-PUFAs) has been reported to ameliorate the progression of NAFLD. The aim of our study was to investigate the impact of dietary n-3-PUFA enrichment on the development of NAFLD and liver lipidome. Mice were fed for 6 weeks either a high-fat methionine choline-deficient diet (MCD) or standard chow with or without n-3-PUFAs. Liver histology, serum biochemistry, detailed plasma and liver lipidomic analyses, and genome-wide transcriptome analysis were performed. Mice fed an MCD developed histopathological changes characteristic of NAFLD, and these changes were ameliorated with n-3-PUFAs. Simultaneously, n-3-PUFAs decreased serum triacylglycerol and cholesterol concentrations as well as ALT and AST activities. N-3-PUFAs decreased serum concentrations of saturated and monounsaturated free fatty acids (FAs), while increasing serum concentrations of long-chain PUFAs. Furthermore, in the liver, the MCD significantly increased the hepatic triacylglycerol content, while the administration of n-3-PUFAs eliminated this effect. Administration of n-3-PUFAs led to significant beneficial differences in gene expression within biosynthetic pathways of cholesterol, FAs, and pro-inflammatory cytokines (IL-1 and TNF-α). To conclude, n-3-PUFA supplementation appears to represent a promising nutraceutical approach for the restoration of abnormalities in liver lipid metabolism and the prevention and treatment of NAFLD.

Accumulation of lipotoxic lipids, such as free cholesterol, induces hepatocyte death and subsequent inflammation and fibrosis in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the underlying mechanisms remain unclear. We have previously reported that hepatocyte death locally induces phenotypic changes in the macrophages surrounding the corpse and remnant lipids, thereby promoting liver fibrosis in a murine model of NASH. Here, we demonstrated that lysosomal cholesterol overload triggers lysosomal dysfunction and profibrotic activation of macrophages during the development of NASH. β-cyclodextrin polyrotaxane (βCD-PRX), a unique supramolecule, is designed to elicit free cholesterol from lysosomes. Treatment with βCD-PRX ameliorated cholesterol accumulation and profibrotic activation of macrophages surrounding dead hepatocytes with cholesterol crystals, thereby suppressing liver fibrosis in a NASH model, without affecting the hepatic cholesterol levels. In vitro experiments revealed that cholesterol-induced lysosomal stress triggered profibrotic activation in macrophages predisposed to the steatotic microenvironment. This study provides evidence that dysregulated cholesterol metabolism in macrophages would be a novel mechanism of NASH.

The prevalence of overweight and obesity are well known risk factors of atherosclerotic cardiovascular disease (ASCVD). We aimed to examine the association between body mass index (BMI) and ASCVD over a 23-year follow-up in young adults. We also qualified how much of the effects of obesity on ASCVD were mediated through blood pressure, cholesterol, and glucose.

Data are from the Korean Life Course Health Study, a cohort study of 226,955 Korean young adults aged 20-39. At baseline, the participants undertook routine health assessments where their BMI was measured in 1992-1994; and the metabolic mediators including systolic blood pressure (SBP), fasting serum glucose (FSG), and total cholesterol (TC) were re-measured in 2002-2004. The main outcomes of the study include incident events of ischemic heart disease (IHD), stroke, and ASCVD between 2005 and 2015. Cox proportional model was used to calculate adjusted hazard ratios (HRs) for ASCVD.

In both men and women, the direct effect of BMI on ASCVD was greater than the indirect effect. The percentage of excess HR of BMI mediated by all of the metabolic mediators, including SBP, FSG, and TC, was 45.7% for stroke and 18.7% for IHD in men and 27.5% for stroke and 17.6% for IHD in women.

High BMI in young adults increases the risk of metabolic mediators in their middle age, and metabolic mediators explain the adverse effects of high BMI on stroke risk than IHD risk.

Findings on the role of diet in non-alcoholic fatty liver disease (NAFLD) pathogenesis are inconsistent. There are few studies on the dietary habits of pregnant women with NAFLD. Our primary aim was to compare the dietary intakes of pregnant women with and without NAFLD.

This case-control study recruited 60 women (26-34 weeks' gestation) with recently diagnosed gestational diabetes (GDM) before any treatment was implemented. At recruitment, all participants underwent B-mode hepatic ultrasound. We included 30 women with sonographic NAFLD (cases) and 30 women without NAFLD (controls) matched for age, skin color, and pre-pregnancy body mass index. We assessed participants' dietary intakes in the last six months using a validated food frequency questionnaire. Mann-Whitney´s test was used to compare differences in median macro and micronutrient intakes between cases and controls.

Total median daily energy (1965.1 × 1949.2 calories) and lipid (25.1% × 28.3%) intakes were similar in women with and without NAFLD and fell within recommended ranges. Participants with NAFLD reported significantly higher median daily intakes of carbohydrates (59.4% × 53.1% p = 0.003), and significantly lower protein (15.6% × 17.0% p = 0.005), fiber (10.7 × 13.3 g/day p = 0.010), and vitamin C (151.8 × 192.6 mg/day p = 0.008) intakes than those without NAFLD.

Pregnant women with NAFLD ingest more carbohydrates and less protein, fiber, and vitamin C than those without NAFLD. Our findings contribute to understanding the role of diet in the development of NAFLD in pregnant women.

Obesity is a heterogenous disease accompanied by a broad spectrum of cardiometabolic risk profiles. Traditional paradigms for dietary weight management do not address biological heterogeneity between individuals and have catastrophically failed to combat the global pandemic of obesity-related diseases. Nutritional strategies that extend beyond basic weight management to instead target patient-specific pathophysiology are warranted. In this narrative review, we provide an overview of the tissue-level pathophysiological processes that drive patient heterogeneity to shape distinct cardiometabolic phenotypes in obesity. Specifically, we discuss how divergent physiology and postprandial phenotypes can reveal key metabolic defects within adipose, liver, or skeletal muscle, as well as the integrative involvement of the gut microbiome and the innate immune system. Finally, we highlight potential precision nutritional approaches to target these pathways and discuss recent translational evidence concerning the efficacy of such tailored dietary interventions for different obesity phenotypes, to optimise cardiometabolic benefits.

Non-alcoholic fatty liver disease is highly prevalent in the bariatric population but not all patients develop liver fibrosis. Considering that fibrosis may affect clinical outcomes, it is important to assess and treat contributing factors. In this population, it is not clear whether dietary intake is a contributor. The objective was to determine the relationship between dietary intake components and liver fibrosis before and 1 y after Roux-en-Y gastric bypass (RYGB).

This was a prospective cross-sectional (n = 133) study conducted between 2013 and 2022. In addition, a subgroup of 44 patients were followed for 1 y post-RYGB. Anthropometrics, biochemical measurements, and 3-d food records and liver biopsies were obtained presurgery and, in a subgroup of patients, as for the cohort, 1 y post-RYGB.

In the cross-sectional study, 78.2% were female, with a median age of 48 y and body mass index of 46.8 kg/m2; 33.8% had type 2 diabetes mellitus and 57.1% had metabolic syndrome. In a multivariate analysis, age (odds ratio; 95% CI) (1.076; 1.014-1.141), alanine transaminase (1.068; 1.025-1.112), calorie intake (1.001; 1.000-1.002), and dietary copper (0.127; 0.022-0.752) were independently associated with fibrosis (<0.05). At 1 y post-RYGB, no independent risk factors were associated with persistent fibrosis.

In bariatric patients before surgery, higher age, alanine transaminase, and total calorie and lower copper intakes were independent risk factors associated with liver fibrosis. These relationships were no longer observed after RYGB, likely due to the effect of surgery on weight and similar postsurgery diet among patients.

We hypothesized that fatty liver disease (FLD) is associated with a high prevalence of hearing loss (HL) owing to metabolic disturbances. This study aimed to evaluate the association between FLD and HL in a large sample of the Korean population.

We used a dataset of adults who underwent routine voluntary health checkups (n=21,316). Fatty liver index (FLI) was calculated using Bedogni's equation. The patients were divided into two groups: the non-FLD (NFLD) group (n=18,518, FLI <60) and the FLD group (n=2,798, FLI ≥60). Hearing thresholds were measured using an automatic audiometer. The average hearing threshold (AHT) was calculated as the pure-tone average at four frequencies (0.5, 1, 2, and 3 kHz). HL was defined as an AHT of >40 dB.

HL was observed in 1,370 (7.4%) and 238 patients (8.5%) in the NFLD and FLD groups, respectively (p=0.041). Compared with the NFLD group, the odds ratio for HL in the FLD group was 1.16 (p=0.040) and 1.46 (p<0.001) in univariate and multivariate logistic regression analyses, respectively. Linear regression analyses revealed that FLI was positively associated with AHT in both univariate and multivariate analyses. Analyses using a propensity score-matched cohort showed trends similar to those using the total cohort.

FLD and FLI were associated with poor hearing thresholds and HL. Therefore, active monitoring of hearing impairment in patients with FLD may be helpful for early diagnosis and treatment of HL in the general population.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease without pharmacological treatment yet. There is also a lack of specific dietary recommendations and strategies to treat the negative health impacts derived from NAFLD.

This scoping review aimed to compile dietary patterns, foods, and nutrients to ameliorate NAFLD.

A literature search was performed through MEDLINE, Scopus, Web of Science, and Google Scholar.

Several guidelines are available through the literature. Hypocaloric Mediterranean diet is the most accepted dietary pattern to tackle NAFLD. Coffee consumption (sugar free) may have a protective effect for NAFLD. Microbiota also plays a role in NAFLD; hence, fibre intake should be guaranteed.

A high-quality diet could improve liver steatosis. Weight loss through hypocaloric diet together with physical activity and limited sugar intake are good strategies for managing NAFLD. Specific dietary recommendations and a Mediterranean plate have been proposed to ameliorate NAFLD.

Dietary macronutrients are essential for metabolic regulation and insulin function. The present study examined the effects of different high-fat diets (HFDs) and high-carbohydrate diets (HCDs) on the development of non-alcoholic fatty liver disease and metabolic syndrome indices in healthy adult male Wistar albino rats. Forty-two rats were distributed into six groups (n = 7), which were fed the following for 22 weeks: (1) a control diet; (2) a high-carbohydrate, low-fat diet (HCD-LFD); (3) high-saturated-fat, low-carbohydrate diet (HSF-LCD); (4) a high-monounsaturated-fat diet (HMUSF); (5) a high medium-chain fat diet (HMCF); and a (6) a high-carbohydrate, high-fiber diet (HCHF). In comparison to the control, the body weight increased in all the groups. The HSF-LCD group showed the highest levels of cholesterol, triglyceride, low-density lipoprotein, hepatic enzyme, insulin resistance, and Homeostatic Model Assessment for Insulin Resistance. A liver histology analysis of the HSF-LCD group showed macrovesicular hepatic steatosis associated with large hepatic vacuolation. Additionally, it showed marked periportal fibrosis, especially around the blood vessels and blood capillaries. The lowest levels of fasting glycemia, insulin, and HOMA-IR were observed in the HCHF group. In conclusion, these findings show that dietary saturated fat and cholesterol are principal components in the development and progression of non-alcoholic fatty liver disease in rats, while fiber showed the greatest improvement in glycemic control.

Secondary sarcopenia develops as a result of a bedridden state and illnesses, such as cachexia, liver disease, and diabetes. However, there is a lack of animal models to investigate the underlying mechanisms and potential treatments for secondary sarcopenia. Recently, secondary sarcopenia has been associated with the prognosis of nonalcoholic steatohepatitis. This study aimed to investigate whether stroke-prone spontaneously hypertensive rat 5 (SHRSP5/Dmcr) which developed severe nonalcoholic steatohepatitis by a high-fat and high-cholesterol (HFC; containing 2% cholic acid) diet is a useful model of secondary sarcopenia.

SHRSP5/Dmcr rats were divided into 6 groups fed with a Stroke-Prone (SP: normal chow) or HFC diets for different periods (4, 12, and 20 weeks), and WKY/Izm rats were divided into 2 groups fed an SP or HFC diet. Body weight, food intake, and muscle force were measured weekly for all rats. After the end of the diet period, skeletal muscle strength evoked by electrical stimulation was recorded, blood was collected, and organ weight was measured. The sera were used for biochemical analysis and the organs were used for histopathological analysis.

SHRSP5/Dmcr rats fed an HFC diet developed nonalcoholic steatohepatitis, and their skeletal muscles, especially fast muscles, showed atrophy, indicating that muscle atrophy is aggravated by the progression of nonalcoholic steatohepatitis. In contrast, WKY/Izm rats fed an HFC diet did not exhibit sarcopenia.

This study suggests that SHRSP5/Dmcr rats could be a useful novel model for investigate the mechanism of secondary sarcopenia disorder associated with nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with an estimated prevalence of 25% globally. NAFLD is closely associated with metabolic syndrome, which are both becoming increasingly more common with increasing rates of insulin resistance, dyslipidemia, and hypertension. Although NAFLD is strongly associated with obesity, lean or nonobese NAFLD is a relatively new phenotype and occurs in patients without increased waist circumference and with or without visceral fat. Currently, there is limited literature comparing and illustrating the differences between lean/nonobese and obese NAFLD patients with regard to risk factors, pathophysiology, and clinical outcomes. In this review, we aim to define and further delineate different phenotypes of NAFLD and present a comprehensive review on the prevalence, incidence, risk factors, genetic predisposition, and pathophysiology. Furthermore, we discuss and compare the clinical outcomes, such as insulin resistance, dyslipidemia, hypertension, coronary artery disease, mortality, and progression to nonalcoholic steatohepatitis, among lean/nonobese and obese NAFLD patients. Finally, we summarize the most up to date current management of NAFLD, including lifestyle interventions, pharmacologic therapies, and surgical options.