Management Of Nonalcoholic Fatty Liver Disease Research Articles

Clinical cohort of nonalcoholic fatty liver disease in a primary care setting

ABSTRACT Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is increasingly common, and primary care physicians (PCPs) are often the first to diagnose NAFLD. While guidelines on NAFLD management in primary care exist, there are limited data on clinical practice patterns. Approach: We gathered data from over 370,000 patients with at least one PCP visit between July 2016 and September 2023. Using ICD-10 codes to identify patients with a diagnosis of NAFLD or Nonalcoholic Steatohepatitis (NASH), we extracted demographics, comorbidities, laboratory results, prescriptions, imaging orders, and referrals to describe their care. Results: We identified 10,334 patients with a diagnosis code of NAFLD (93.1%) and/or NASH (16.7%) during a PCP visit. Just over half (54.8%) were female, mean age was 52.8 years, and mean BMI was 33.2 kg/m2 with 90% having overweight or obese. More than 50% had hypertension and hyperlipidemia, and 38% had diabetes. At the diagnosis visit, 2.7% had ultrasound elastography ordered, 2.7% liver biopsy, and less than 1% magnetic resonance elastography. During follow-up ranging from 0 to 7 years, patients had a mean of 15 encounters, during which 4% were diagnosed with fibrosis or cirrhosis. Only 24.2% of patients were referred to a nutritionist and 18% had an appointment, and only 0.7% were referred to hepatology and 3.8% saw a hepatologist. Conclusion: PCPs have not widely implemented clinical practice guidelines for NAFLD, resulting in suboptimal care including for the substantial minority with fibrosis or cirrhosis. Patients might benefit from targeted NAFLD education for PCPs and improved decision and management support.

The effect of myo‐inositol supplementation on AMPK/PI3K/AKT pathway and insulin resistance in patients with NAFLD

AbstractInsulin resistance (IR) is the pivotal pathological hit in non‐alcoholic fatty liver disease (NAFLD). There is specific attention to combination/conjugated therapies for NAFLD management. As myo‐inositol (MI) has been shown to improve IR in animal and human trials, this study aimed to investigate the influence of MI supplementation on glycemic response and IR through AMPK/PI3K/AKT signaling pathway in obese patients with NAFLD. This double‐blinded placebo‐controlled randomized clinical trial was conducted on 48 obese (BMI = 30–40 kg/m2) patients with NAFLD who were randomly assigned to receiving either MI (4 g/day) or placebo (maltodextrin 4 g/day) group for 8 weeks. Before and after the trial, weight, height, serum glycemic parameters (inc. fasting glucose and insulin) as well as IR indices were assessed. Moreover, the mRNA expression levels of AMPK, AKT, and PDK‐1 in peripheral blood mononuclear cells (PBMCs) were determined. MI supplementation resulted in significant increases in the fold changes of AMPK, AKT, and PDK‐1 genes (p = .019, p = .049, and p = .029, respectively). Indeed, IR improved in terms of all IR indices in MI group (p < .05) after adjusting for the confounders, apart from quantitative insulin sensitivity check index (QUICKI). The results showed that MI supplementation not only upregulated AMPK, AKT, and PDK‐1 mRNA in PBMCs but also improved IR in obese patients with NAFLD.

Survey of physicians' knowledge about pediatric nonalcoholic fatty liver disease in China.

To evaluate physicians' awareness and knowledge towards pediatric nonalcoholic fatty liver disease (NAFLD) and their attitude toward change in nomenclature from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) in China. The questionnaire survey contained five parts (characteristics of the participants, epidemiology, diagnosis, management of NAFLD, and attitudes toward the nomenclature of MAFLD/MASLD). The participants included 53 hepatologists, 88 gastroenterologists (GEs), 74 endocrinologists (ENDOs), 61 primary care physicians (PCPs), and 157 pediatricians across 31 municipalities, provinces and autonomous regions of China's mainland. Hepatologists saw the largest number of pediatric NAFLD patients annually (median 9 [range 1-20]), with the lowest number by PCPs (even notwithstanding one patient annually). The primary sources of pediatric NAFLD knowledge were acquired via guidelines. Hepatologists had the highest total knowledge score among all five types of physicians. Approximately one-third of nonspecialists (ENDOs and PCPs) considered liver biopsy necessary for pediatric NAFLD patients, and this percentage increased to half in specialists (hepatologists and GEs). For nonspecialists, the major barriers to the management of pediatric NAFLD were poor patient adherence to lifestyle modifications and lacking confidence in managing NAFLD. Above 90% physicians agreed to change the nomenclature NAFLD to MAFLD; however, they were not sure whether it could reduce the economic burden. Despite the epidemic of pediatric NAFLD in China, a significant knowledge gap remains in the identification, diagnosis, and treatment of pediatric NAFLD, particularly among frontline workers such as pediatricians and PCPs. More education programs should be carried out in the future.

MiR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

Analysis of Probiotic Role in Non-Alcoholic Fatty Liver Disease (NAFLD) Management: A Meta-Analysis

Background: Non-alcoholic fatty liver disease (NAFLD) is an increasing global health problem. Probiotics have emerged as a potential therapy for NAFLD, but evidence for their efficacy remains mixed. This meta-analysis aims to evaluate the effectiveness of probiotics in the management of NAFLD. Methods: A comprehensive literature search was performed on PubMed, Embase, Cochrane Library, and Web of Science databases until December 2023. Randomized controlled trials (RCTs) evaluating the effects of probiotics in NAFLD patients were included. The main outcomes evaluated were changes in liver enzymes (ALT, AST), insulin resistance index (HOMA-IR), and hepatic steatosis score. Meta-analysis was performed using a random effects model, and heterogeneity was assessed using the I² statistic. Results: Twenty-five RCTs involving 1845 patients met inclusion criteria. Meta-analysis showed that probiotics significantly reduced ALT (MD -8.45; 95% CI -12.67 to -4.23; p<0.0001) and AST (MD -6.89; 95% CI -10.11 to -3.67; p<0.0001) levels compared with placebo. Significant reductions were also observed in HOMA-IR (MD -0.68; 95% CI -1.02 to -0.34; p<0.0001) and hepatic steatosis scores (SMD -0.45; 95% CI -0.71 to -0.19; p=0.0008). Subgroup analysis showed that the effects of probiotics were more pronounced in patients with NAFLD non-alcoholic steatohepatitis (NASH) and those receiving multi-strain probiotics. Conclusion: This meta-analysis provides strong evidence that probiotics have beneficial effects on biochemical and imaging parameters in NAFLD patients. Probiotics may be considered as an adjunct therapy for NAFLD, especially in patients with NASH. However, more research is needed to determine the optimal probiotic strain, dosage, and duration of treatment.

The efficacy and safety of Dachaihu decoction in the treatment of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD), also known as metabolic associated fatty liver disease (MAFLD), is a common liver condition characterized by excessive fat accumulation in the liver which is not caused by alcohol. The main causes of NAFLD are obesity and insulin resistance. Dachaihu decoction (DCHD), a classic formula in traditional Chinese medicine, has been proved to treat NAFLD by targeting different aspects of pathogenesis and is being progressively used in the treatment of NAFLD. DCHD is commonly applied in a modified form to treat the NAFLD. In light of this, it is imperative to conduct a systematic review and meta-analysis to assess the effectiveness and safety of DCHD in the management of NAFLD. There is a need for a systematic review and meta-analysis to assess the effectiveness and safety of modified DCHD in treating NAFLD. The objective of this meta-analysis was to systematically assess the clinical effectiveness and safety of DCHD in treating NAFLD. This meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Including seven databases, both Chinese and English databases were searched for relevant studies. The quality of included studies was carefully assessed using the bias risk assessment tool in the Cochrane Handbook. Eligible articles were the source of extracted data which was meta-analyzed by using Review Manager 5.4 and Stata 17.0. A total of 10 studies containing 825 patients were included. Compared with conventional treatments, combined treatment could clearly improve the liver function of NAFLD patients, which could reduce the levels of ALT (MD = -7.69 U/L, 95% CI: -11.88 to -3.51, p < 0.001), AST (MD = -9.58 U/L, 95% CI: -12.84 to -6.33, p < 0.01), and it also had a certain impact on regulating lipid metabolism, which could reduce the levels of TC (MD = -0.85 mmol/L, 95% CI: -1.22 to 0.48, p < 0.01), TG (MD = -0.45 mmol/L, 95% CI: -0.64 to 0.21, p < 0.01). Adverse event showed that DCHD was relatively safe. Due to the inclusion of less than 10 trials in each group, it was not possible to conduct a thorough analysis of publication bias. According to the meta-analysis, in the treatment of the NAFLD, it is clear that the combination of DCHD was advantages over conventional treatment alone in improving liver function, regulating lipid metabolism. Additionally, DCHD demonstrates a relatively safe profile. Nevertheless, due to limitations in the quality and quantity of the studies incorporated, the effectiveness and safety of DCHD remain inconclusive. Consequently, further high-quality research is imperative to furnish more substantial evidence supporting the widespread clinical application of DCHD. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023397353, CRD42023397353.

Metformin use review in Non-Alcoholic Fatty Liver Disease (NFLDA) and students survey

This study presented the literature review findings and the knowledge and opinions of 41 first-year pharmacy students regarding metformin's role in managing non-alcoholic fatty liver disease (NAFLD), achieving a 92% response rate. NAFLD, affecting about a quarter of the global population, is linked with obesity, high cholesterol, and diabetes, presenting a substantial public health issue. Metformin, known for treating type 2 diabetes, is considered for NAFLD management due to its potential in improving insulin sensitivity and reducing hepatic gluconeogenesis. Survey results, analyzed using SPSS software, showed varied perceptions across demographics. Younger participants (18-24) were more familiar with metformin than older counterparts. Females were more inclined towards recommending metformin for NAFLD, understanding its benefits better than males. Notably, employed individuals and those residing outside certain states demonstrated greater awareness of metformin, suggesting regional knowledge disparities. Participants with a 4-year degree displayed enhanced familiarity with metformin's application in NAFLD. The findings highlight the need for targeted educational efforts to bridge knowledge gaps about metformin and NAFLD management among pharmacy students. This knowledge is crucial for informing curriculum enhancements and integrating NAFLD management into therapeutic courses or modules for aspiring healthcare professionals. Significant associations were identified between students' age, gender, employment status, residency, income level, and their understanding of metformin, indicating diverse educational needs.

Non-alcoholic fatty liver disease in type 2 diabetes: Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies.

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, affecting more than half of the people living with type 2 diabetes (T2D). The relationship between NAFLD and T2D is bidirectional and the presence of one perpetuates the other, which significantly increases the hepatic as well as extrahepatic complications. Until recently, there was no approved pharmacological treatment for NAFLD/ nonalcoholic steatohepatitits (NASH). However, there is evidence that drugs used for diabetes may have beneficial effects on NAFLD. Insulin sensitizers acting through peroxisome proliferator-activated receptor (PPAR) modulation act on multiple levels of NAFLD pathogenesis. Pioglitazone (PPARγ agonist) and saroglitazar (PPARα/γ agonist) are particularly beneficial and recommended by several authoritative bodies for treating NAFLD in T2D, although data on biopsy-proven NASH are lacking with the latter. Initial data on elafibanor (PPAR α/δ agonist) and Lanifibranor (pan PPAR agonist) are promising. On the other hand, incretin therapies based on glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and dual- and triple-hormone receptor co-agonists reported impressive weight loss and may have anti-inflammatory and antifibrotic properties. GLP-1 RAs have shown beneficial effects on NAFLD/NASH and more studies on potential direct effects on liver function by dual- and triple-agonists are required. Furthermore, the long-term safety of these therapies in NAFLD needs to be established. Collaborative efforts among healthcare providers such as primary care doctors, hepatologists, and endocrinologists are warranted for selecting patients for the best possible management of NAFLD in T2D.

Interpretation of the 2024 American Diabetes Association guidelines for the comprehensive management of non-alcoholic fatty liver disease combined with diabetes mellitus

Non-alcoholic fatty liver disease (NAFLD) is a common concomitant disease in adults with type 2 diabetes mellitus (T2DM) and prediabetes. Therefore, T2DM/NAFLD patient populations are at high risk for cardiovascular disease. The occurrence and progression of non-alcoholic fatty liver disease-related liver fibrosis and cardiovascular disease have a severe impact on the patient's prognosis and mortality rate. The American Diabetes Association's 2024 "Guidelines for the Standardized Management of Diabetes" put forward recommendations relevant to the screening, evaluation, treatment, and management of NAFLD in T2DM and prediabetic populations, as well as liver fibrosis. The important measures for decelerating liver inflammation and fibrosis progression and the risk of cardiovascular disease are based on improvements in lifestyle methods, weight loss, and blood sugar control.

Evaluation of health practices among individuals with non-alcoholic fatty liver disease: A randomized controlled trial

The current strategy for addressing non-alcoholic fatty liver disease (NAFLD) emphasizes lifestyle adjustments aimed at promoting weight loss. Recommendations include dietary changes and regular physical activity to support patients with NAFLD in achieving their weight loss objectives. However, there is a lack of comprehensive data assessing the efficacy of these approaches. In this randomized controlled trial (RCT) encompassing 90 meticulously chosen individuals diagnosed with NAFLD, participants were divided into intervention (n = 45) and control (n = 45) groups. Across a duration of six months, the intervention consisted of a customized dietary and exercise program designed specifically for NAFLD management, which was implemented, with pre-and post-tests conducted at the beginning and at the end of 6 months. The findings revealed that, the intervention led to improvements in health practices, particularly within the intervention group as compared to the control group, underscoring its significance in managing NAFLD.

Multifunctional role of oral bacteria in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders of varying severity, ultimately leading to fibrosis. This spectrum primarily consists of NAFL and non-alcoholic steatohepatitis. The pathogenesis of NAFLD is closely associated with disturbances in the gut microbiota and impairment of the intestinal barrier. Non-gut commensal flora, particularly bacteria, play a pivotal role in the progression of NAFLD. Notably, Porphyromonas gingivalis, a principal bacterium involved in periodontitis, is known to facilitate lipid accumulation, augment immune responses, and induce insulin resistance, thereby exacerbating fibrosis in cases of periodontitis-associated NAFLD. The influence of oral microbiota on NAFLD via the "oral-gut-liver" axis is gaining recognition, offering a novel perspective for NAFLD management through microbial imbalance correction. This review endeavors to encapsulate the intricate roles of oral bacteria in NAFLD and explore underlying mechanisms, emphasizing microbial control strategies as a viable therapeutic avenue for NAFLD.

Association between Dietary Quality and Non-Alcoholic Fatty Liver Disease in Korean Adults: A Nationwide, Population-Based Study Using the Korean Healthy Eating Index (2013-2021).

This study explored the relationship between the Korean Healthy Eating Index (KHEI) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included 34,174 Korean adults. The KHEI was composed of three subcomponents (adequacy, moderation, and energy balance) and calculated based on a 24 h dietary recall. The total score ranged from 0 to 100, with a higher score indicating a greater adherence to the Korean dietary guidelines. The total KHEI scores were categorized into quartiles (Q1-Q4). NAFLD was classified using the hepatic steatosis index. Logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The adjusted OR (95% CI) of NAFLD was 0.95 (0.87-1.03) for the Q2 group, 0.90 (0.83-0.98) for the Q3 group, and 0.79 (0.72-0.87) for the Q4 group, compared with the Q1 group. Among the subcomponents of the KHEI, individuals with high scores in the adequacy component, characterized by an abundant consumption of fruits, vegetables, and dairy products, exhibited the most pronounced association with NAFLD. A higher KHEI score was negatively associated with NAFLD in Korean adults. Therefore, the promotion of healthy dietary patterns can play a beneficial role in the prevention or management of NAFLD.

Current Management of Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of other causes of liver fat accumulation. The prevalence of NAFLD is increasing and now among top causes of hepatocellular carcinoma. The diagnosis of NAFLD requires evidence from liver biopsy. There are currently no specific drugs for therapy of NAFLD. Current mainstay for management of NAFLD is lifestyle interventions focused around weight loss. Lifestyle interventions can be done by dietary modification or increasing physical activity level. Pioglitazone and vitamin E are only recommended for patient whom was confirmed NAFLD by liver biopsy. New agents such as obeticholic acid, elafibranor, selonsertib, and cenicriviroc are still waiting for phase III result to be recommended as therapy for NAFLD. Bariatric surgery can be advised for NAFLD patient with obesity who is not adequately controlled by medical therapy.

Controlled attenuation parameter (CAP): the clinical value based on MRI-PDFF in children with obesity.

Controlled attenuation parameter (CAP) is a noninvasive and quantitative method to evaluate hepatic steatosis, which is not well evaluated in children. The aim ofthis study was to examine the diagnostic value of CAP forhepatic steatosis in children with obesity based on MR proton density fat fraction (PDFF). About 108 pediatric patients with nonalcoholic fatty liver disease (NAFLD) who were assessed for PDFF, CAP, and other laboratory results were enrolled. In this study, pediatric patients were separated for the obese group (n=80) and the severe obese group (n=28). Hepatic steatosis grades (0-3) were classified according to PDFF using cutoff values of 6.4 , 17.4, and 22.1 %. There are significant differences in CAP between the obese and severe obese groups (p<0.05). CAP showed a good correlation with PDFF in pediatric patients with NAFLDfor diagnosing hepatic steatosis using a cutoff valueof 265 dB/m (p<0.001). Meanwhile, ALT significantly outperforms CAP in receiver-operating curve (ROC) analysis for diagnosing hepatic steatosis grades. The diagnostic accuracy of CAP for steatosis is 77.8 %, and the diagnostic accuracy of ALT for steatosis is 83.3 %. While CAP holds promise as a diagnostic tool for pediatric NAFLD, its diagnostic performance warrants some caution. The potential of CAP is evident; however, ALTemerges as a simpler and more accurate measure for detecting hepatic steatosis in children. Further research is essential to determine the optimal role of CAP in pediatric NAFLD diagnosis and management.

Study the Physiological and Biochemical Effects of Berberine Extract on Nonalcoholic Fatty Liver Disease (NAFLD) in Male Rabbits

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global health issue, characterized by hepatic steatosis and associated with metabolic comorbidities such as obesity, diabetes, and dyslipidemia. Berberine (BBR), an isoquinoline alkaloid, has emerged as a potential therapeutic agent for NAFLD. In this research, we evaluated the effects of BBR on NAFLD management and its associated complications. Our analysis included three groups involving 10 rabbits induced NAFLD by administration cholesterol rich diet, 10 rabbits administrated high rich diet with fats and cholesterol, and 10 rabbits with normal fed as control group. BBR demonstrated significant improvements in liver function biochemical markers (ALT, AST, GGT), lipid indices (TC, TG, LDL-C, HDL-C), and physiological parameters such as insulin sensitivity (HOMA-IR) and body mass index (BMI). Importantly, BBR exhibited a favorable safety profile, with minimal gastrointestinal adverse events reported. These findings highlight BBR potential as an adjunct therapy for NAFLD. However, further well-designed clinical trials involving human subjects are warranted to validate its efficacy and safety.

Non-alcoholic fatty liver disease among patients undergoing ultra-sonography abdomen and its associated factors in a tertiary care hospital, Kakinada

Background: Non-alcoholic fatty liver disease (NAFLD) presents a growing global health concern, characterized by the accumulation of hepatic lipids in the absence of significant alcohol consumption. Its prevalence has surged worldwide, including in India, where it has reached alarming levels. Despite its silent progression, NAFLD can lead to severe complications, including liver cirrhosis and hepatocellular carcinoma. Objectives of the study to assess prevalence and its associated factors, which are essential for effective management and prevention strategies. Methods: An observational, analytical cross-sectional study was conducted in a tertiary care hospital in Kakinada, Andhra Pradesh, from June to July 2022. Among 100 subjects, chosen through the simple random sampling. Ethical approval was granted before conducting study. Data on demographics, lifestyle risk factors, anthropometry, and ultrasound findings were collected using a pretested and validated case record form. Statistical analysis was carried out using SPSS software, employing appropriate tests to explore associations between NAFLD and various variables. Results: Among 100 participants, the prevalence of NAFLD was found to be 41%. Significant associations were observed between NAFLD and variables such as BMI (p=0.034), waist-hip ratio (p=0.002), and history of diabetes mellitus (p=0.000). Lifestyle factors, including increased cooking oil consumption, were identified as significant risk factors. Conclusions: The study highlights the high prevalence of NAFLD among subjects undergoing ultrasound abdomen in Kakinada. Significant associations were observed with BMI, waist-hip ratio, and diabetes mellitus history. Promoting healthy behaviours is crucial for NAFLD prevention and management.

Bioprotective Role of Phytocompounds Against the Pathogenesis of Non-alcoholic Fatty Liver Disease to Non-alcoholic Steatohepatitis: Unravelling Underlying Molecular Mechanisms.

Non-alcoholic fatty liver disease (NAFLD), with a global prevalence of 25%, continues to escalate, creating noteworthy concerns towards the global health burden. NAFLD causes triglycerides and free fatty acids to build up in the liver. The excessive fat build-up causes inflammation and damages the healthy hepatocytes, leading to non-alcoholic steatohepatitis (NASH). Dietary habits, obesity, insulin resistance, type 2 diabetes, and dyslipidemia influence NAFLD progression. The disease burden is complicated due to the paucity of therapeutic interventions. Obeticholic acid is the only approved therapeutic agent for NAFLD. With more scientific enterprise being directed towards the understanding of the underlying mechanisms of NAFLD, novel targets like lipid synthase, farnesoid X receptor signalling, peroxisome proliferator-activated receptors associated with inflammatory signalling, and hepatocellular injury have played a crucial role in the progression of NAFLD to NASH. Phytocompounds have shown promising results in modulating hepatic lipid metabolism and de novo lipogenesis, suggesting their possible role in managing NAFLD. This review discusses the ameliorative role of different classes of phytochemicals with molecular mechanisms in different cell lines and established animal models. These compounds may lead to the development of novel therapeutic strategies for NAFLD progression to NASH. This review also deliberates on phytomolecules undergoing clinical trials for effective management of NAFLD.

Essential Oils for the Treatment and Management of Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD), characterized by excessive liver fat accumulation, is a common liver disease linked to obesity, insulin resistance, and metabolic dysfunction. The lack of effective treatments against NAFLD has led to an increasing focus on alternative and natural remedies. Essential oils, extracted from a variety of plants, have drawn interest due to their high content of active compounds and potential functions to support liver health. Ginger essential oil, known for its anti-inflammatory, antioxidant, and cholesterol-lowering properties, promotes antioxidant enzymes and ameliorates liver fat accumulation in mice model of NAFLD. Nigella sativa oil with its diverse array of bioactive components, mitigates fatty liver by lowering tumor necrosis factor-alpha, malonaldehyde (MDA), and plasma lipids in vivo and in human trials that could contribute to NAFLD management. Garlic oil, rich in organosulfur compounds, has shown potential benefits in modulating oxidative stress and inflammation associated with NAFLD. Similarly, essential oils from turmeric, pepper, patchouli, and basil reduced lipid accumulation and inflammation and enhanced lipid metabolism in animal models of NAFLD. These findings underscore the use of essential oils as complementary medicines for NAFLD, opening avenues for further research and clinical applications.

17β-Estradiol protects female rats from bilateral oophorectomy-induced nonalcoholic fatty liver disease induced by improving linoleic acid metabolism alteration and gut microbiota disturbance

After surgical or natural menopause, women face a high risk of nonalcoholic fatty liver disease (NAFLD), which can be diminished by hormone replacement therapy (HRT). The gut microbiota is subject to modulation by various physiological changes and the progression of diseases. This microbial ecosystem coexists symbiotically with the host, playing pivotal roles in immune maturation, microbial defense mechanisms, and metabolic functions essential for nutritional and hormone homeostasis. E2 supplementation effectively prevented the development of NAFLD after bilateral oophorectomy (OVX) in female rats. The changes in the gut microbiota such as abnormal biosynthetic metabolism of fatty acids caused by OVX were partially restored by E2 supplementation. The combination of liver transcriptomics and metabolomics analysis revealed that linoleic acid (LA) metabolism, a pivotal pathway in fatty acids metabolism was mainly manipulated during the induction and treatment of NAFLD. Further correlation analysis indicated that the gut microbes were associated with abnormal serum indicators and different LA metabolites. These metabolites are also closely related to serum indicators of NAFLD. An in vitro study verified that LA is an inducer of hepatic steatosis. The changes in transcription in the LA metabolism pathway could be normalized by E2 treatment. The metabolic perturbations of LA may directly and secondhand impact the development of NAFLD in postmenopausal individuals. This research focused on the sex-specific pathophysiology and treatment of NAFLD, providing more evidence for HRT and calling for the multitiered management of NAFLD.

Hypercaloric low-carbohydrate high-fat diet protects against the development of nonalcoholic fatty liver disease in obese mice in contrast to isocaloric Western diet.

Obesity and metabolic complications, such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD), are one of the greatest public health challenges of the 21st century. The major role of high sugar and carbohydrate consumption rather than caloric intake in obesity and NAFLD pathophysiology remains a subject of debate. A low-carbohydrate but high-fat diet (LCHFD) has shown promising results in obesity management, but its effects in preventing NAFLD need to be detailed. This study aims to compare the effects of a LCHFD with a high-fat high-sugar obesogenic Western diet (WD) on the progression of obesity, type 2 diabetes, and nonalcoholic fatty liver disease. Male C57BL/6J mice were initially fed a WD for 10 weeks. Subsequently, they were either switched to a LCHFD or maintained on the WD for an additional 6 weeks. Hepatic effects of the diet were explored by histological staining and RT-qPCR. After the initial 10 weeks WD feeding, LCHF diet demonstrated effectiveness in halting weight gain, maintaining a normal glucose tolerance and insulin levels, in comparison to the WD-fed mice, which developed obesity, glucose intolerance, increased insulin levels and induced NAFLD. In the liver, LCHFD mitigated the accumulation of hepatic triglycerides and the increase in Fasn relative gene expression compared to the WD mice. Beneficial effects of the LCHFD occurred despite a similar calorie intake compared to the WD mice. Our results emphasize the negative impact of a high sugar/carbohydrate and lipid association for obesity progression and NAFLD development. LCHFD has shown beneficial effects for NAFLD management, notably improving weight management, and maintaining a normal glucose tolerance and liver health.