The present study explored the association between biological aging (BA), healthy eating index-2015 (HEI-2015) and non-alcoholic fatty liver disease (NAFLD) in the general population of the United States.

We used data from the NHANES database between 2017-2018 years to conduct the study. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS), and subgroup analysis were performed to analyze the association of BA and HEI-2015 with prevalence of NAFLD and the mediation effect of HEI-2015 was also discussed. Additionally, generalized additive model was conducted to investigate the association of BA and HEI-2015 with ZJU index, BARD score, and NAFLD fibrosis score.

There was a total of 2,421 individuals. RCS shown that BA was positively correlated with prevalence of NAFLD, while HEI-2015 was negative correlated with NAFLD risk. After adjusting for interfering factors, compared with the lowest quartiles of BA and HEI-2015, the odds ratios with 95% confidence intervals for NAFLD across the quartiles were (1.24 (0.84, 1.84), 2.07 (1.15, 3.73) and 2.49 (1.16, 5.38)) and (0.89 (0.66, 1.18), 0.87 (0.65, 1.16) and 0.64 (0.46, 0.87)), respectively. The BA was linear positive with ZJU index, BARD score and NAFLD fibrosis score. However, the linear negative correlation existed between HEI-2015 and ZJU index, BARD score and NAFLD fibrosis score. Mediation analysis showed that the positive correlation between BA and NAFLD could be mediated and weakened by HEI-2015.

The prevalence of NAFLD gradually increases with BA, but this positive association can be weakened by the healthy diet.

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.

Excessive intake of fatty acids is a key factor contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of saturated fatty acids (SFA) and unsaturated fatty acids (UFA) on the development of MASLD are uncertain. Therefore, we conducted two-sample Mendelian randomization studies and animal experiments to explore the effects of SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the risk of developing MASLD.

The genetic summary data of exposures and outcome were retrieved from genome-wide association studies (GWASs) and used for five Mendelian randomization methods. A comprehensive sensitivity analysis was performed to verify the robustness of the results. Mice were subjected to different diets followed by assessment of severity of steatosis based on a histological score and determination of hepatic triglyceride levels to investigate the relationships between SFA, MUFA, PUFA and MASLD.

The Mendelian randomization results showed that MUFA (odds ratio: 1.441, 95% confidence interval: 1.078-1.927, P = 0.014) was causally associated with the incidence of MASLD. SFA and PUFA were not causally associated with the incidence of MASLD. Sensitivity analysis did not identify any significant bias in the results. The animal experiment results showed that a MUFA-enriched diet significantly contributed to the development of hepatic steatosis (P < 0.001).

SFA and PUFA did not have a significant causal effect on MASLD, but MUFA intake is a risk factor for MASLD. A MUFA-enriched diet increased the incidence of macrovesicular steatosis and the hepatic triglyceride levels. Therefore, replacing MUFA intake with a moderate intake of PUFA might help reduce the risk of MASLD.

Numerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to explore the causal relationship between MASLD and GERD in European and East Asian populations.

This study utilized a bidirectional, two-sample Mendelian randomization (MR) approach. All disease data were obtained from the GWAS database, and single nucleotide polymorphisms strongly associated with exposure were selected as instrumental variables. The inverse variance weighted (IVW) method is primarily utilized to evaluate the causal relationship between exposure and outcome. Finally, sensitivity analyses were performed to ensure the robustness of the results.

The IVW estimates indicated that non-alcoholic fatty liver disease (NAFLD) (odds ratio (OR) = 1.054, 95% confidence interval (CI), 0.966-1.150, p = 0.236) and percent liver fat (OR = 0.977, 95% CI, 0.937-1.018, p = 0.258) in European population were not linked to a higher risk of GERD. However, GERD in European population was associated with an increased risk of NAFLD (OR = 1.485, 95% CI, 1.274-1.729, p < 0.001) and percent liver fat (OR = 1.244, 95% CI, 1.171-1.321, p < 0.001). In addition, the IVW analysis in East Asian population showed that alanine aminotransferase (ALT) was associated with an increased risk of GERD (OR = 2.305, 95% CI, 1.241-4.281, p = 0.008), whereas aspartate aminotransferase (AST) had no causal effects on GERD risk (OR = 0.973, 95% CI, 0.541-1.749, p = 0.926). Furthermore, the associations between GERD and ALT (OR = 1.007, 95% CI, 0.998-1.015, p = 0.123) or AST (OR = 1.004, 95% CI, 0.997-1.012, p = 0.246) were not significant. After removing outliers, a significant correlation between GERD and ALT was observed (OR = 1.009, 95% CI, 1.001-1.016, p = 0.020).

There was reverse causality between MASLD and GERD in European population, while there was bidirectional causality between a proxie for MASLD (ALT) and GERD in East Asian population. This study can provide novel insights into cross-ethnic genetic research on MASLD and GERD.

The global prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has increased. In addition to childhood obesity, environmental risk factors, such as heavy metals that are known to be involved in hepatotoxicity, play role in NAFLD occurrence. However, their association with NAFLD remains unclear. This study aimed to investigate the association between heavy metal exposure and NAFLD biomarkers in adolescents.

In this cross-sectional study, we used the data of a total of 1505 adolescents aged 12-17 years who participated in the Korean National Environmental Health Survey III (2015-2017) and IV (2018-2020). The presence of blood lead (BPb), blood mercury (BHg), urinary mercury (UHg), and urinary cadmium (UCd) were measured. Liver enzymes including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were evaluated. For NAFLD biomarkers, the hepatic steatosis index (HSI) was calculated. Multivariate linear regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) model were used to investigate the association between heavy metals and NAFLD biomarkers.

Among heavy metals, mercury presence showed a significant association with NAFLD biomarkers. Two-fold increases in BHg and UHg were associated with 0.21 points (95 % confidence interval [CI]: 0.08-0.35) and 0.19 points (95 % CI: 0.09-0.30) higher HSI, respectively. In the WQS model, heavy metal mixture was significantly associated with increased HSI (β = 0.06, 95 % CI: 0.01-0.11). Similarly, in the BKMR model, heavy metal mixture was positively associated with NAFLD biomarkers, and BHg was the most important contributor in the association.

BHg and UHg were significantly associated with NAFLD biomarkers in adolescents, indicating that organic and inorganic mercury exposure could potentially be a risk factor for NAFLD. To mitigate and address the risk of NAFLD associated with heavy metal exposure, it is imperative to take measure to reduce avoidable mercury exposure is necessary.

Nutrition is associated with tuberculosis drug-induced liver injury (TBLI). How dietary patterns relate to tuberculosis drug-induced liver injury is still unknown. The objective of this study is to explore the relation between dietary patterns and the risk of tuberculosis drug-induced liver injury.

This cohort study was conducted at two hospitals in Shandong Province, China, between 2011 and 2013. A total of 605 tuberculosis patients were included in the final analysis. The blood aspartate aminotransferase or alanine aminotransferase level was monitored through the 6-month tuberculosis treatment. The semi-quantitative food frequency questionnaires were used to survey dietary intake in the second month of the tuberculosis treatment. The China Healthy Diet Index (CHDI), which was previously validated in the Chinese population, was used as an a priori dietary pattern. A posteriori dietary patterns were extracted by principal component analysis (PCA).

The CHDI was negatively associated with the risk of liver injury [adjusted odds ratio (aOR) per standard deviation (SD) (95% CI): 0.61 (0.40-0.94)] and liver dysfunction [aOR per SD (95% CI): 0.47 (0.35-0.64)] in the multivariate logistic model. A positive association between "Organ meat, poultry, and vegetable oil" dietary pattern scores (extracted by PCA) and the risk of liver injury [aOR (95% CI): 3.02 (1.42-6.41)] and liver dysfunction [aOR (95% CI): 1.83 (1.09-3.05)] was observed.

In conclusion, a high CHDI score was a protective factor for tuberculosis drug-induced liver injury, while the "Organ meat, poultry, and vegetable oil" dietary pattern, which was rich in organ meat, poultry, and vegetable oil and low in vegetables, was an independent risk factor for tuberculosis drug-induced liver injury.

In the United States, 10.2% households (HH) report child food insecurity. We assessed associations between metabolic dysfunction-associated fatty liver disease (MASLD) and food insecurity among the adolescents in the United States.

This cross-sectional study was performed using data from the National Health and Nutrition Examination Survey 2017-2018. Food insecurity was assessed by the US Department of Agriculture Child Food Security Survey Module. MASLD was defined by transient elastography.

Among 771 adolescents (aged 12-18 years) (mean age 14.7 years; 52.5% male; 50.9% White, 12.7% Black, 24.4% Hispanic, and 12.1% other), 9.8% reported food insecurity; MASLD prevalence of 10.12% (95% confidence interval [CI] 7.13%-13.20%) affecting 4.27 million adolescents; and nonalcoholic fatty liver disease prevalence of 10.77% (95% CI 7.76-13.78) affecting 4.52 million adolescents. There was near-perfect concordance between MASLD and nonalcoholic fatty liver disease (Cohen's κ coefficient of 0.971, 95% CI 0.946-0.996). The prevalence of MASLD was greater among food-insecure adolescents vs food-secure ones (17.4% vs 9.4%) and adolescents living with a low HH income vs those with a higher HH income (15.0% vs 7.2%) and living with a head of HH with a lower education level vs one with a higher education level (18.0% vs 8.2%) ( P < 0.05). The fully adjusted model showed that compared with adolescents living in a higher HH income, food-insecure adolescents living in low income HH had a 3-fold greater risk (odds ratio [OR] 3.25, 1.31-8.08) of having MASLD, while food-secure adolescents living in low-income HH had no increased risk (OR 1.58, 0.85-2.93, P = 0.139). The fully adjusted odds of having MASLD was elevated by +163% with the presence of HTN (OR 2.63, 1.02-6.78), +241% with being Hispanic (OR 3.41, 1.36-8.56), and +138% with being male (OR 2.38, 1.20-4.75). In addition, a 1-unit increase in BMI was associated with 25% increase in the odds of having MASLD (OR 1.25, 1.17-1.33) among US adolescents.

Food insecurity is associated with MASLD among US low-income adolescents especially Hispanic male individuals with obesity and hypertension. Policies addressing inequities are needed.

This study was designed to compare the effects of four meal patterns on liver steatosis, fibrosis, and biochemical factors in patients with Nonalcoholic fatty liver disease (NAFLD).

The 12-week intervention was performed on 123 patients with NAFLD who were randomly allocated into four groups: "3-meals", "skipping breakfast", "skipping dinner", and " 3 meals and 3 snacks per day." group. The assessment of liver steatosis, fibrosis, biochemical factors, and anthropometrical evaluation were performed at baseline and at end of the study.

A significant improvement was found in the liver steatosis and fibrosis among the patients who consumed 3 meals, 3 snacks compared to the other groups (P < 0.001). In addition, a higher reduction was observed in serum levels of alanine amino transferase (ALT) (20.93 ± 23.37 mg/dl, P < 0.001), aspartate aminotransferase (AST) (17.15 ± 16.48 mg/dl, P < 0.001), gamma-glutamyl transferase(GGT) (13.43 ± 13.41 mg/dl; P < 0.001), and alkaline phosphatase (ALK) (47.19 ± 60.51 mg/dl; P = 0.004) in patients who consumed 3 meals, 3 snacks, while the concentration of liver enzymes in patients who consumed 3 meals increased significantly. At the end of the study, there was a significant increase in the fasting blood sugar (FBS) concentration in the "skipping breakfast" group (17.51 ± 38.85 mg/dl; P = 0.011) and "3-meals" group (17.51 ± 38.85 mg/dl, P = 0.03).

Consuming 3 meals, 3 snack per day significantly improves disease severity and biochemical factors in NAFLD patients. Further studies are warranted.

: IRCT20201010048982N2. Name of the registry: Urmia University of Medical Sciences. Date of registration: 2021-08-22, 1400/05/31. URL of trial registry record: https://www.irct.ir/search/result?query=IRCT20201010048982N2.

The online version contains supplementary material available at 10.1007/s40200-023-01375-2.

This editorial builds on the article titled "Establishment and validation of an adherence prediction system for lifestyle interventions in non-alcoholic fatty liver disease" by Zeng et al. We carried out a critical examination of nonalcoholic fatty liver disease (NAFLD) pathogenesis and how lifestyle interventions could facilitate disease resolution, particularly highlighting that non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD. Our discussion details that weight loss is a pivotal factor in disease outcomes: A 3%-5% reduction is enough for resolution in 50% of non-obese individuals, while a 7%-10% reduction achieves similar benefits in obese individuals, as demonstrated by magnetic resonance spectroscopy. Additionally, the editorial underscores that such lifestyle changes are instrumental not only in resolving NAFLD but also in reversing hepatic steatosis and inflammation. These insights, derived from the research, emphasize the critical role of personalized lifestyle modifications in halting the progression of NAFLD to NASH and even reversing fibrosis, thus offering a template for effective patient management.

Consumption of diets high in sugar and fat is related to the development of Metabolic dysfunction-associated steatotic liver disease (MASLD). Carnosine (CAR) is a dipeptide with antioxidant and anti-inflammatory action and has been studied for treating diseases. This work aimed to evaluate the effects of CAR on diet-induced MASLD in rats. Male Wistar rats were distributed into 2 groups (17 weeks): normocaloric (Co, n = 12), and hypercaloric diet rich in lipids and simple carbohydrates (MASLD, n = 12). After, the animals were redistributed to begin the treatment with CAR (4 weeks): Co (n = 6), Co + CAR (n = 6), MASLD (n = 6), and MASLD + CAR (n = 6), administered intraperitoneally (250 mg/kg). Evaluations included nutritional, hormonal and metabolic parameters; hepatic steatosis, inflammatory and oxidative markers. MASLD group had a higher adiposity index, systolic blood pressure, glucose, plasma and liver triglycerides and cholesterol, insulin, hepatic steatosis, oxidative markers, and lower PPAR-α (Peroxisome Proliferator-activated receptor α), compared to the Co. CAR attenuated plasma and hepatic triglyceride and cholesterol levels, hepatic steatosis, CD68+ macrophages, and hepatic oxidative markers, in addition to increasing HDL cholesterol levels and PPAR-α, compared to the untreated MASLD group. CAR acts in importants pathophysiological processes of MASLD and may be a therapeutic compound to control the disease.

The coronavirus disease 2019 (COVID-19) pandemic clearly affected the lifestyle and dietary habits of millions of people worldwide. The purpose of this study was to evaluate the association of major dietary patterns with socioeconomic status, obesity, and contracting COVID-19.

We conducted a cross-sectional study using an online survey for data collection with a total of 1,187 participants (over the age of 18 years) who reported their sociodemographic details, anthropometric index (weight and height), and dietary intake. Multivariable logistic regression models were applied to assess the association between major dietary patterns and study outcomes.

A total of 1,106 adults were included in the current analysis. We identified three major dietary patterns (plant-based, meat, and Western dietary patterns). The mean age of participants was significantly higher in the upper tertile of plant-based dietary patterns (DPs) compared to the first tertile, while it was lower in the top tertile of meat and Western DPs. The percentage of participants who lived in urban areas was significantly higher in the third tertile of meat DP than in the first tertile (p < 0.001). Moderate adherence to Western DP was significantly associated with increased odds of obesity (OR: 1.79; 95% CI: 1.17, 2.74). In addition, high adherence to Western DP was significantly related to increased odds of obesity after controlling for confounders. Subjects in the second tertile of the Western DP had higher odds (95% Cl: 1.04, 1.92) for COVID-19 infection than the first tertile.

This study showed that moderate and high adherence to a Western dietary pattern was associated with a higher risk of obesity and COVID-19 infection during the pandemic. Future studies are needed to confirm these findings.

Non-alcoholic steatohepatitis (NASH) is emerging as a major cause of hepatocellular carcinoma (HCC), however, it is not resolved if compounds in late-stage clinical development for NASH may have additional therapeutic benefits in NASH-driven HCC (NASH-HCC). Here, we profiled monotherapy with semaglutide (glucagon-like-receptor-1 receptor agonist) and lanifibranor (pan-peroxisome proliferator-activated receptor agonist) in a diet-induced obese (DIO) mouse model of NASH-HCC. Disease progression was characterized in male C57BL/6 J mice fed the GAN (Gubra Amylin NASH) diet high in fat, fructose and cholesterol for 12-72 weeks (n = 15 per group). Other GAN DIO-NASH-HCC mice fed the GAN diet for 54 weeks and with biopsy-confirmed NASH (NAFLD Activity Score ≥ 5) and advanced fibrosis (stage F3) received vehicle (n = 16), semaglutide (30 nmol/kg, s.c., n = 15), or lanifibranor (30 mg/kg, p.o., n = 15) once daily for 14 weeks. GAN DIO-NASH-HCC mice demonstrated progressive NASH, fibrosis and HCC burden. Tumors presented with histological and molecular signatures of poor prognostic HCC. Consistent with clinical trial outcomes in NASH patients, both lanifibranor and semaglutide improved NASH while only lanifibranor reduced fibrosis in GAN DIO-NASH-HCC mice. Notably, only semaglutide reduced tumor burden in GAN DIO-NASH-HCC mice. In conclusion, the GAN DIO-NASH-HCC mouse is a clinical translational model of NASH-HCC. Semaglutide improves both NASH and tumor burden in GAN DIO-NASH-HCC mice, highlighting the suitability of this preclinical model for profiling novel drug therapies targeting NASH-HCC.

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.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese.

We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD.

The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0-3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides.

High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment.

The liver is the leading site for lipid metabolism, involving not only fatty acid beta-oxidation but also de novo synthesis of endogenous triglycerides and ketogenesis. The liver maintains systemic lipid homeostasis by regulating lipid synthesis, catabolism, and transportation. Dysregulation of hepatic lipid metabolism precipitates disorders, such as non-alcoholic fatty liver disease (NAFLD), affecting the whole body. Thus, comprehending and studying hepatic lipid metabolism is crucial for preventing and treating metabolic liver diseases. Traditionally, researchers have investigated the impact of a single nutrient on hepatic lipid metabolism. However, real-life dietary patterns encompass diverse nutrients rather than single components. In recent years, there have been increased studies and notable progress regarding the effects of distinct dietary patterns on hepatic lipid metabolism. This review summarizes the influence of diverse dietary patterns on hepatic lipid metabolism, elucidating underlying molecular mechanisms and appraising the therapeutic potential of dietary patterns in managing hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD), which is linked to western diet (WD) intake, affects 30% of the world's population and involves the crosstalk of liver steatosis, hypertrophy/inflammation of adipose tissue and deregulation of gut microbiome. Glyphosate and 2,4-D are some of the most applied herbicides worldwide, and their roles in NAFLD have not been investigated. Thus, the present study evaluated whether glyphosate and 2,4-D, in single or mixed exposure, alter WD-induced NAFLD in a mouse model. Male C57Bl/6 mice (n = 10/group) received a fat (30% lard, 0.02% cholesterol), and sucrose-rich diet (20%) and high sugar solution (23.1 and 18.9 g/L of fructose and glucose) for 6 months. Simultaneously, animals received glyphosate (0.05 or 5 mg/kg/day), 2,4-D (0.02 or 2 mg/kg/day), or their combination (0.05 +0.02 or 5 +2 mg/kg/day) by intragastrical administration (5 ×/week). Doses were based on the Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) levels. Herbicide exposures featured differential responses. WD-induced obesity, hypercholesterolemia, and hyperglycemia remained unaltered. Compared to the group receiving only WD, only the concomitant exposure to WD and 2,4-D (2 mg) enhanced the percentage of mice with moderate/severe hepatic inflammation, CD68 macrophage infiltration, and malondialdehyde levels in the liver. In line, this herbicide modulated immune response- (including Cd4, C8b, Cd28, Cxcr3, Cxcr6) and oxidative stress-related (such as Gsta1, Gsta2, Gsta4, Gstm1, Gstm2, Gstm3, Gstm4, Nqo1, Gpx2) genes in the hepatic transcriptome analysis. This exposure also enriched pro-inflammatory Deferribacteres phylum in fecal microbiome. In general, the herbicide mixtures did not feature the same effects attributed to 2,4-D isolated exposure. Our findings indicate that 2,4-D, at a dose within the toxicological limits, was able to induce disturbances in mainly at the liver and gut axes involved in NAFLD development in male mice.

Childhood obesity is on the rise worldwide increasing the risk for metabolic, cardiovascular and liver diseases in children. Eating habits and lifestyle changes are currently the standard of care for treating pediatric obesity. Our study aimed to determine the impact of a dietary intervention based on the Mediterranean Diet (MD) and the Health Eating Plate, on anthropometric and metabolic parameters in obese and overweight boys.

We studied 126 overweight/obese boys with anthropometric measurements, blood biochemistry and nutrient intakes evaluation by means of Food Frequency Questionnaire (FFQ) at baseline, at 6 and 12 months after a nutritional-behavioral intervention.

We observed a significant reduction in energy, macronutrients and micronutrients intakes. BMI-SDS significantly decreased after 1 year with the proportion of obese boys decreasing by 33% and of overweight boys by 41%, while also all fat mass measures decreased both in obese and overweight individuals. In obese boys, ALT decreased significantly after 1-year nutritional intervention and these changes correlated with BMI-SDS reduction. Insulin-resistance and secretion indexes correlated with fat mass and BMI-SDS. In obese boys, significant changes were observed at 6 months for insulin concentrations, 1/HOMA-IR and QUICKI. With regard to the lipid profile, significant decreases were observed for total and LDL cholesterol in obese boys.

Metabolic and anthropometric risk factors in overweight and obese boys can be improved by a nutritional-behavioral intervention of 1-year duration.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identification of factors contributing to the onset and progression of NAFLD have the potential to direct novel strategies to combat NAFLD.

We examined the time course of western diet (WD)-induced NAFLD and its progression to nonalcoholic steatohepatitis (NASH) in age-matched female and male Ldlr-/- mice, with time-points at 1, 4, 8, 20 and 40 weeks on the WD. Controls included Ldlr-/- mice maintained on a purified low-fat diet (LFD) for 1 and 40 weeks. The approach included quantitation of anthropometric, plasma and liver markers of disease, plus hepatic histology, lipids, oxylipins, gene expression and selected metabolites.

One week of feeding the WD caused a significant reduction in hepatic essential fatty acids (EFAs: 18:2, ω6, 18:3, ω3) which preceded the decline in many C20-22 ω3 and ω6 polyunsaturated fatty acids (PUFA) and PUFA-derived oxylipins after 4 weeks on the WD. In addition, expression of hepatic inflammation markers (CD40, CD44, Mcp1, Nlrp3, TLR2, TLR4, Trem2) increased significantly in both female & male mice after one week on the WD. These markers continued to increase over the 40-week WD feeding study. WD effects on hepatic EFA and inflammation preceded all significant WD-induced changes in body weight, insulin resistance (HOMA-IR), oxidative stress status (GSH/GSSG ratio) and histological and gene expression markers of macrosteatosis, extracellular matrix remodeling and fibrosis.

Our findings establish that feeding Ldlr-/- mice the WD rapidly lowered hepatic EFAs and induced key inflammatory markers linked to NASH. Since EFAs have an established role in inflammation and hepatic inflammation plays a major role in NASH, we suggest that early clinical assessment of EFA status and correcting EFA deficiencies may be useful in reducing NASH severity.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a global public health risk. The occurrence of adolescent NAFLD coincides with high rates of overweight and obesity, with an unhealthy lifestyle also playing a role. Data on prevalence and factors contributing to NAFLD among Asian adolescents is lacking as most studies focus on adults. This systematic review aims to determine the prevalence and factors contributing to NAFLD among adolescents.

A systematic search was conducted using five (Goh et al., 2013) [5] databases: Cochrane, PubMed, Scopus, Science Direct, EBSCO and grey literature. Two reviewers independently screened studies using predefined inclusion and exclusion criteria and performed data extraction. Assessment of methodological quality was completed using the Newcastle-Ottawa checklist.

The quality of most studies were of high quality, with the majority reporting no association between lifestyle factors and NAFLD. A total of 6 studies were included in this systematic review. The prevalence of NAFLD among adolescents varied between 8.0% (Fraser et al., 2007) in a study on 5586 adolescents aged 12-19 and 16.0% (Chen et al., 2009) in another survey of 1724 adolescents aged 12-13 years old. Snacking habits and lack of physical activity had potential associations with adolescent NAFLD. Current evidence shows that lifestyle factor (Western dietary pattern) is associated with a higher risk of developing NAFLD among adolescents.

Lifestyle factors, including snacking habits and lack of physical activity, were associated with a higher risk of developing NAFLD among adolescents from high-income countries. The difference in the prevalence of NAFLD between countries with different incomes requires further investigation.

An increasing number of studies have evaluated the association between ultra-processed foods (UPF) consumption and metabolic disorders. However, the association between UPF intake and non-alcoholic fatty liver disease (NAFLD) remains unclear. In this study, we analysed data from 6545 participants who were recruited in National Health and Nutrition Examination Surveys 2011-2018. UPF were defined in light of the NOVA food classification system and divided into quartiles based on its proportion of total weight intake. Complex logistic regression models were used to assess the association between UPF and NAFLD. Mediation analyses were conducted to reveal underlying mediators. We found that NAFLD patients consumed more UPF than controls (925·92 ± 18·08 v. 812·70 ± 14·32 g/d, P < 0·001). Dietary intake of UPF (% weight) was negatively related to the Healthy Eating Index-2015 score (Spearman r = -0·32, P < 0·001). In the multivariable model, the highest quartile compared with the lowest, the OR (95 % CI) were 1·83 (1·33, 2·53) for NAFLD (OR per 10 % increment: 1·15; 95 % CI: 1·09, 1·22; P for trend < 0·001) and 1·52 (1·12, 2·07) for insulin resistance (OR per 10 % increment: 1·11; 95 % CI: 1·05, 1·18; P for trend = 0·002). Mediation analyses revealed that poor diet quality, high saturated fat and refined grain intake partly mediated the association between UPF and NAFLD. In conclusion, high UPF intake was associated with an increased risk of NAFLD in US adults. Further prospective studies are needed to verify these findings.

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.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome (MS)-related liver disorder that has an increasing prevalence. Thus, the aim of our study is to evaluate the effects of pomegranate peel extract (PP) supplementation on hepatic status and metabolic syndrome risk factors.

In phase one, the hydro-alcoholic extraction of the peel of 750 kg of pomegranate (Punica granatum L.) was performed by the soaking method. Then, in phase two, NAFLD patients received 1500 mg of placebo (n = 37) or pomegranate peel capsules (n = 39) with a 500-kcal deficit diet for 8 weeks. Gastrointestinal intolerance, dietary intake, lipid and glycemic profiles, systolic and diastolic blood pressure, body composition, insulin resistance indexes, and elastography-evaluated NAFLD changes were followed.

The mean age of participants was 43.1 ± 8.6 years (51.3% female). Following the intervention, the mean body weight (mean changes: -5.10 ± 2.30 kg), waist circumference (-7.57 ± 2.97 cm), body mass index (-1.82 ± 0.85 kg/m2), body fat index (-1.49 ± 0.86), and trunk fat (- 3.93 ± 3.07%), systolic (-0.63 ± 0.29 cmHg) and diastolic (-0.39 ± 0.19 cmHg) blood pressure, total cholesterol (-10.51 ± 0.77 mg/dl), triglyceride (-16.02 ± 1.7 mg/dl), low-density lipoprotein cholesterol (-9.33 ± 6.66 mg/dl; all P < 0.001), fat free mass (- 0.92 ± 0.90 kg; P < 0.003), and fasting blood sugar (-5.28 ± 1.36 mg/dl; P = 0.02) decreased significantly in PP in contrast to the placebo group in the raw model and when adjusted for confounders. Also, high-density lipoprotein cholesterol (5.10 ± 0.36 mg/dl), liver steatosis and stiffness (- 0.30 ± 0.17 and - 0.72 ± 0.35 kPa, respectively, all P < 0.001) improved in the PP group. However, fasting insulin (P = 0.81) and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.93) were not significantly different when comparing two groups during the study in the raw and even adjusted models.

In conclusion, 1500 mg pomegranate peel extract along with a weight-loss diet improved metabolic syndrome risk factors and reduced hepatic steatosis in patients with NAFLD after 8 weeks.

Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identifying early gene indicators contributing to the onset and progression of NAFLD has the potential to develop novel targets for early therapeutic intervention. We report on the early and late transcriptomic signatures of western diet (WD)-induced nonalcoholic steatohepatitis (NASH) in female and male Ldlr-/- mice, with time-points at 1 week and 40 weeks on the WD. Control Ldlr-/- mice were maintained on a low-fat diet (LFD) for 1 and 40 weeks.

The approach included quantitation of anthropometric and hepatic histology markers of disease as well as the hepatic transcriptome.

Only mice fed the WD for 40 weeks revealed evidence of NASH, i.e., hepatic steatosis and fibrosis. RNASeq transcriptome analysis, however, revealed multiple cell-specific changes in gene expression after 1 week that persisted to 40 weeks on the WD. These early markers of disease include induction of acute phase response (Saa1-2, Orm2), fibrosis (Col1A1, Col1A2, TGFβ) and NASH associated macrophage (NAM, i.e., Trem2 high, Mmp12 low). We also noted the induction of transcripts associated with metabolic syndrome, including Mmp12, Trem2, Gpnmb, Lgals3 and Lpl. Finally, 1 week of WD feeding was sufficient to significantly induce TNFα, a cytokine involved in both hepatic and systemic inflammation.

This study revealed early onset changes in the hepatic transcriptome that develop well before any anthropometric or histological evidence of NALFD or NASH and pointed to cell-specific targeting for the prevention of disease progression.

Studying human dietary intake may help us identify effective measures to treat or prevent many chronic diseases whose natural histories are influenced by nutritional factors. Here, by examining five cohorts with dietary intake data collected on different time scales, we show that the food intake profile varies substantially across individuals and over time, while the nutritional intake profile appears fairly stable. We refer to this phenomenon as 'nutritional redundancy' and attribute it to the nested structure of the food-nutrient network. This network enables us to quantify the level of nutritional redundancy for each diet assessment of any individual. Interestingly, this nutritional redundancy measure does not strongly correlate with any classical healthy diet scores, but its performance in predicting healthy aging shows comparable strength. Moreover, after adjusting for age, we find that a high nutritional redundancy is associated with lower risks of cardiovascular disease and type 2 diabetes.

Steatosis is the most common liver disease worldwide and the leading cause of liver-associated morbidity and mortality. The aim of this study was to explore the differences in blood parameters and dietary habits in non-obese patients with and without steatosis.

The present study included 987 participants with BMI < 30, assessed in the fourth recall of the MICOL study. Patients were divided by steatosis grade, and a validated food frequency questionnaire (FFQ) with 28 food groups was administered.

The prevalence of non-obese participants with steatosis was 42.86%. Overall, the results indicated many statistically significant blood parameters and dietary habits. Analysis of dietary habits revealed that non-obese people with or without steatosis had similar dietary habits, although higher daily amounts of red meat, processed meat, ready meals, and alcohol were recorded in participants with liver disease (p < 0.05).

Many differences were found in non-obese people with and without steatosis, but in light of a network analysis, the two groups demonstrated similar dietary habits, proving that pathophysiological, genetic, and hormonal patterns are probably the basis of their liver status, regardless of weight. Future genetic analyses will be performed to analyze the expression of genes involved in the development of steatosis in our cohort.

Diet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined.

The purpose of this study was to assess the association of two healthy eating indices with the presence and severity of MAFLD in a sample of Veterans in a primary care setting.

This was a single center cross-sectional study using a random stratified sample of Veterans enrolled in primary care. Participants underwent a Fibroscan and completed an interviewer-administered Diet History Questionnaire II from which we calculated the Healthy Eating Index-2015 and Alternate Mediterranean Diet Score. We used multivariable logistic regression models to assess associations of dietary quality with MAFLD.

We analyzed data from 187 participants, 53.5% of whom were female. On average, participants were 50.2 years of age (SD, 12.3 years) with an average BMI of 31.7 kg/m2. MAFLD was detected in 78 (42%) and at least moderate fibrosis in 12 (6%) participants. We found that the Alternate Mediterranean Diet Score was inversely associated with MAFLD (adjusted OR = 0.85, 95%CI 0.72-1.00), but controlling for BMI and total energy intake attenuated the association (adjusted OR = 0.92, 95%CI 0.74-1.15). We found no statistically significant associations between the Healthy Eating Index-2015 and MAFLD or advanced fibrosis.

We found that the Alternate Mediterranean Diet Score was significantly associated with lower MAFLD risk in Veterans; however, the association was mediated by BMI and total energy intake. A Mediterranean-style diet could potentially help reduce the risk of MAFLD, particularly if it helps control total energy intake and weight.

Dietary diabetes risk reduction score (DDRRs) is inversely associated with a lower risk of type 2 diabetes. Given the importance of the association between body fat and insulin resistance and the effect of diet on these parameters, this study aimed to investigate the association between DDRRS and body composition parameters, including the visceral adiposity index (VAI), lipid accumulation product (LAP), and skeletal muscle mass (SMM). This study was conducted on 291 overweight and obese women aged 18-48 years old recruited from 20 Tehran Health Centers in 2018. The anthropometric indices, biochemical parameters, and body composition were measured. A semi-quantitative food frequency questionnaire (FFQ) was used to calculate DDRRs. Linear regression analysis was used to examine the association between DDRRs and body composition indicators. The mean (SD) age of participants was 36.67 (9.10) years. After adjustment for potential confounders, VAI (β = 0.27, 95% CI = - 0.73, 1.27, Ptrend = 0.052), LAP (β = 8.14, 95% CI = - 10.54, 26.82, Ptrend = 0.069), TF (β = - 1.41, 95% CI = 11.45, 17.30, Ptrend = 0.027), trunk fat percent (TF%) (β = - 21.55, 95% CI = - 44.51, 1.61, Ptrend = 0.074), body fat mass (BFM) (β = - 3.26, 95% CI = - 6.08, - 0.44, Ptrend = 0.026), visceral fat area (VFA) (β = - 45.75, 95% CI = - 86.10, - 5.41, Ptrend = 0.026), waist-to-hip ratio (WHtR) (β = - 0.014, 95% CI = - 0.031, 0.004, Ptrend = 0.066), visceral fat level (VFL) (β = - 0.38, 95% CI = - 5.89, 5.12, Ptrend = 0.064), fat mass index (FMI) (β = - 1.15, 95% CI = - 2.28, - 0.02, Ptrend = 0.048) decreased significantly over tertiles of DDRRs, and also there was no significant association between SMM and DDRRs tertiles (β = - 0.57, 95% CI = - 1.69, 0.53, Ptrend = 0.322). The findings of this study demonstrated that participants with higher adherence to the DDRRs had lower VAI (β = 0.78 vs 0.27) and LAP (β = 20.73 vs 8.14). However, there was no significant association between DDRRs and VAI, LAP and SMM, which are mentioned as the primary outcomes. Future studies with larger sample of both genders are needed to investigate our findings.

The global surge of obesity amongst women of reproductive age has raised concerns surrounding the health consequences for their offspring as there is a formidable link between an obesogenic maternal environment and the developmental programming of metabolic dysfunction in the offspring. Specifically, the offspring of mothers with obesity have a three-fold higher risk of developing metabolic-associated fatty liver disease (MAFLD) compared to the offspring of healthy-weight mothers. Given the burgeoning burden of obesity and its comorbidities, it is essential to focus research efforts on methods to alleviate the intergenerational onset of obesity and MAFLD. This review summarizes the current research surrounding the developmental programming of MAFLD in the offspring of mothers with obesity and examines the potential for weight interventions to prevent such metabolic dysfunction in the offspring. It focuses on the benefits of pre-pregnancy interventional strategies, including dietary and exercise intervention, to ameliorate adverse liver health outcomes in the offspring. The utility and translation of these interventions for humans may be difficult for prospective mothers with obesity, thus the use of pre-pregnancy therapeutic weight loss aids, such as glucagon-like peptide-1 receptor agonists, is also discussed.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in children. Following earlier reports on an increase in the prevalence of childhood obesity, NAFLD is now becoming increasingly common in children. Although no definitive cure exists, early management, early diagnosis, and treatment can reduce its complications. This study aims to determine the effectiveness of the combination of ginger and an anti-inflammatory diet (AID) in children with obesity on fatty liver management. This randomized clinical trial was conducted on 160 children with obesity aged 8-11 years, with a mean (SD) weight of 65.01 (9.67) kg, mean (SD) height of 139.87 (7.37) cm, and mean (SD) body mass index of 33.40 (5.59) kg/m2. The study duration was 12 weeks. Children were divided into four groups: ginger (G), AID, ginger plus an AID (GPA), and control. Ginger capsules comprised 1000 mg of ginger, whereas the AID comprised fruits and vegetables, fish, turkey, and chicken (without skin) with lean meat, omega-3 sources, nuts, legumes, probiotic products, and elimination of inflammatory food. Following the intervention, serum fasting blood sugar and high-sensitivity C-reactive protein levels were significantly decreased in the AID (p = .006 and .002, respectively), G (p = .04 and <.001, respectively), and GPA (p <.001 in both cases, respectively) groups. Further, in the G and GPA groups, there was a significant decrease in body mass index (p = .04 in both cases, respectively), waist circumference (p = .009 and .003, respectively), waist-to-height ratio (p = .02 and .005, respectively), alanine aminotransferase (p = .004 and <.001, respectively), total cholesterol (p = .0002 and .0001, respectively) and low-density lipoprotein-cholesterol (p < .001 and <.001, respectively). Eventually, serum aspartate aminotransferase was decreased (p < .001) and high-density lipoprotein-cholesterol (p = .03) was increased significantly in the GPA group. As a main finding of this study, hepatic steatosis significantly decreased in the G and GPA groups. Ginger supplementation can effectively improve NAFLD in children, and its effectiveness was further increased when combined with an AID.

Fatty liver disease is increasingly common worldwide and is associated with an increased risk of cardiovascular disease (CVD).

This review describes the cardiovascular outcomes, clinical assessment and management as well as the impact of emerging drug treatment on CVD risk.

Patients with fatty liver require CVD risk assessment including consideration of statin therapy. Emerging therapeutic drugs for fatty liver may have both adverse and beneficial effects on CVD risk.

This study aimed to investigate non-alcoholic fatty liver disease (NAFLD) occurrence and factors associated with the disease in phenylketonuria (PKU) patients undergoing exclusive dietary treatment.

This cross-sectional study included 101 adolescents 10 to < 20 years of age with PKU, who were undergoing exclusive dietary treatment and monitored since early diagnosis at a single reference service. Anthropometric and biochemical assessments were performed and food intake was documented, and an ultrasound diagnosis of NAFLD was established. Data were evaluated using the Student's t-test for continuous variables, the chi-square for categorical variables, and logistic regression using the Wald chi-squared test; differences with p < 0.05 were considered to be statistically significant.

NAFLD was detected in 26 (25.7%) teenagers. There was no difference in prevalence between the sexes or nutritional status. The final logistic regression model revealed low sensitivity (26.1%) and high specificity (94.7%). The specificity suggested a lower likelihood of NAFLD in older adolescents, in the presence of normal or high levels of alkaline phosphatase, lower carbohydrate intake, and adequate protein and lipid intake.

The prevalence of NAFLD in adolescents with PKU was higher than that found in healthy Brazilian adolescents and similar to that found in obese Brazilian children, suggesting a higher risk for NAFLD in patients with PKU treated exclusively by dietary modification.

A healthy lifestyle during adolescence is associated with insulin sensitivity or liver enzyme levels and thus might contribute to the prevention of non-alcoholic fatty liver disease (NAFLD). Therefore, we examined the association between adherence to a hypothesis-based lifestyle score including dietary intake, physical activity, sedentary behaviour, sleep duration and BMI in adolescence and fatty liver indices in early adulthood. Overall, 240 participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed study completed repeated measurements of lifestyle score factors during adolescence (females: 8·5-15·5 years, males: 9·5-16·5 years). Multivariable linear regression models were used to investigate the association between adolescent lifestyle scores and NAFLD risk (hepatic steatosis index (HSI) and fatty liver index (FLI)) in early adulthood (18-30 years). Participants visited the study centre 4·9 times during adolescence and achieved on average 2·8 (min: 0·6, max: 5) out of five lifestyle score points. Inverse associations were observed between the lifestyle score and fatty liver indices (HSI: ß=-5·8 % (95 % CI -8·3, -3·1), P < 0·0001, FLI: ß=-32·4 % (95 % CI -42·9, -20·0), P < 0·0001) in the overall study population. Sex-stratified analysis confirmed these results in men, while inverse but non-significant associations were observed in women (P > 0·05). A higher lifestyle score was associated with lower HSI and FLI values, suggesting that a healthy lifestyle during adolescence might contribute to NAFLD prevention, predominantly in men. Our findings on repeatedly measured lifestyle scores in adolescents and their association with NAFLD risk in early adulthood warrant confirmation in larger study populations.

Dietary patterns can holistically provide insights into the association of food groups and nutrients with the disease. Several studies have evaluated the association of dietary patterns with the risk of non-alcoholic fatty liver disease (NAFLD) in Western populations. However, few studies focused on this topic were conducted on Korean adults. Therefore, in this cohort study, we aimed to investigate the association between dietary patterns and the risk of NAFLD among middle-aged Koreans.

The survey was performed at general hospitals and health examination centres in Korea. Dietary intake was assessed using a validated Food Frequency Questionnaire. The dietary patterns were identified using principal component analysis. The HR and 95% CI for NAFLD for each of the quartiles of the three dietary patterns were estimated using a Cox proportional hazards model.

South Korean Community.

44 460 healthy Koreans (aged 40-69 years) who completed a follow-up survey from 2012 to 2016 in the Health Examinees study were included.

Men and women following a prudent pattern showed a 22% and 36% lower NAFLD risk, respectively (men: HR=0.78; women: HR=0.64). Men and women who highly adhered to the flour-based food and meat pattern had a 29% and 55% higher NAFLD risk, respectively (men: HR=1.29; women: HR=1.55).

The prudent pattern induced a lower NAFLD risk, whereas the flour-based food and meat pattern induced a higher NAFLD risk. No significant difference was found between the white rice pattern and NAFLD risk.

Large longitudinal studies exploring the role of dietary patterns in the assessment of long-term outcomes of NAFLD are still lacking. We conducted a prospective analysis of 128,695 UK Biobank participants. Cox proportional hazards models were used to estimate the risk associated with two dietary patterns for long-term outcomes of NAFLD. During a median follow-up of 12.5 years, 1925 cases of end-stage liver disease (ESLD) and 12,466 deaths occurred in patients with NAFLD. Compared with patients in the lowest quintile, those in the highest quintile of the diet quality score was negatively associated with the risks of ESLD and all-cause mortality (HRQ5vsQ1: 0.76, 95% CI: 0.66−0.87, p < 0.001; HRQ5vsQ1: 0.84, 95% CI: 0.79−0.88, p < 0.001, respectively). NAFLD patients with high-quality carbohydrate patterns carried a 0.74-fold risk of ESLD and a 0.86-fold risk of all-cause mortality (HRQ5vsQ1: 0.74, 95% CI: 0.65−0.86, p < 0.001; HRQ5vsQ1: 0.86, 95% CI: 0.82−0.91, p < 0.001, respectively). For prudent dietary patterns rich in vegetables, fruits and fish, the adjusted HR Q5vsQ1 (95% CI) was 0.87 (0.76−0.99) and 0.94 (0.89−0.99) for ESLD and all-cause mortality of NAFLD patients. There was a U-shaped association between the meat-rich dietary pattern and all-cause mortality in patients with NAFLD. These findings suggest that a diet characterized by a high-quality, high intake of vegetables, fruits, fish and whole grains as well as an appropriate intake of meat, was associated with a lower risk of adverse outcomes of NAFLD.

Hepatic steatosis is a major health issue that can be attenuated by a healthy diet. This study investigates the effects and molecular mechanisms of butyrate, a dietary fiber metabolite of gut microbiota, on lipid metabolism in hepatocytes.

This study examines the effects of butyrate (0-8 mM) on lipid metabolism in primary hepatocytes. The results show that butyrate (2 mM) consistently inhibits lipogenic genes and activates lipid oxidation-related gene expression in hepatocytes. Furthermore, butyrate modulates lipid metabolism genes, reduces fat droplet accumulation, and activates the calcium/calmodulin-dependent protein kinase II (CaMKII)/histone deacetylase 1 (HDAC1)-cyclic adenosine monophosphate response element binding protein (CREB) signaling pathway in the primary hepatocytes and liver of wild-type (WT) mice, but not in G-protein-coupled receptor 41 (GPR41) knockout and 43 (GPR43) knockout mice. This suggests that butyrate regulated hepatic lipid metabolism requires GPR41 and GPR43. Finally, the study finds that dietary butyrate supplementation (5%) ameliorates hepatic steatosis and abnormal lipid metabolism in the liver of mice fed a high-fat and fiber-deficient diet for 15 weeks.

This work reveals that butyrate improves hepatic lipid metabolism through the GPR41/43-CaMKII/HDAC1-CREB pathway, providing support for consideration of butyrate as a dietary supplement to prevent the progression of NAFLD induced by the Western-style diet.

Dietary fat intake has long been associated with fatty liver. Our study aimed to determine the effect of dietary fats on longitudinal fatty liver index (FLI) trajectories from adolescence to young adulthood.

Nine hundred eighty-five participants in the Raine Study, Perth, Western Australia, Australia, had cross-sectional assessments at ages 14, 17, 20 and 22 years, during which anthropometric measurements and blood tests were obtained. FLI trajectories were derived from the longitudinal FLI results. Dietary fat intake was measured with a semi-quantitative food frequency questionnaire at 14 years and log multinominal regression analyses were used to estimate relative risks.

Three FLI trajectories were identified and labelled as stable-low (79.1%, N = 782), low-to-high (13.9%, N = 132), and stable-high (7%, N = 71). The low-to-high group associated with an increased intake of the long-chain polyunsaturated fatty acids EPA, DPA and DHA (RR 1.27, 95% CI 1.10-1.48) relative to the stable-low group. Compared to the stable-low group, omega-6 and the ratio of omega-6 to omega-3 in the stable-high group were associated with an increased relative risk of 1.34 (95% CI 1.02-1.76) and 1.10 (95% CI 1.03-1.16), respectively.

For those at high risk of fatty liver in early adolescence, high omega-6 fatty acid intake and a high ratio of omega-6 to omega-3 fatty acids are associated with increased risk of fatty liver. There should be caution in assuming these associations are causal due to possible undetected and underestimated confounding factors.

Non-alcoholic fatty liver disease (NAFLD) is defined as the excessive accumulation of fat in the liver cells of people who do not drink alcohol. The aim of study is investigated the association between low carbohydrate diets (LCDs) and NAFLD.

This age and gender-matched case-control study was conducted on 120 patients newly diagnosed with NAFLD and 120 adults without NAFLD. Diagnosis of NAFLD based on laboratory tests and abdominal ultrasound. Low carbohydrate diets score calculated on the percentage of energy as carbohydrate, fat, and protein. Participants in the highest rank intake of fat and protein and lowest intake of carbohydrate received 10 points. Multivariable logistic odds ratio was used for examine the relation between LCDs and NAFLD.

This study showed subjects in the highest tertile of LCD has more intake of zinc and vitamin B12 compare to lowest. Also, intake of protein (p = 0.02) carbohydrate (p < 0.02) and cholesterol (p = 0.02) were significantly higher in patient with NAFLD compare to control subjects. There was no significant association between LCD and risk of NAFLD (OR: 1.36; 95% CI: 0.97-1.92; P-trend = 0.13) in crude and adjusted (OR: 1.31; 95% CI: 0.84-2.04; P-trend = 0.23) model.

However, we showed that intake of protein, carbohydrate and cholesterol are higher in NAFLD, but our results of study showed that LCDs with higher proportion intakes of protein and fat was not associated with NAFLD. Further prospective studies are required for confirm these associations.

There is little evidence for the associations of the overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) with the odds of nonalcoholic fatty liver disease (NAFLD). We present a nationwide cross-sectional study among US adults aged 18 years or older. Diet was assessed by 24-h recalls. Overall PDI, hPDI, and uPDI were constructed based on 18 food groups. NAFLD was defined based on controlled attenuation parameter derived via transient elastography (TE) in the absence of other causes of chronic liver disease. Among 3900 participants with eligible TE examination, 1686 were diagnosed with NAFLD. The overall PDI was not associated with NAFLD prevalence (comparing extreme tertiles of PDI score OR = 1.03, 95% CI 0.76, 1.38, ptrend = 0.609). However, hPDI was inversely (OR = 0.50, 95% CI 0.35, 0.72, ptrend < 0.001), while uPDI was positively associated with odds of NAFLD (OR = 1.37, 95% CI 0.93, 2.02, ptrend = 0.009) in the multivariable-adjusted models without body mass index (BMI). After further adjustment for BMI, only the association of hPDI with NAFLD remained statistically significant (OR = 0.64, 95% CI 0.46, 0.87, ptrend = 0.006). Such inverse association appeared stronger in non-Hispanic whites, but not in other racial/ethnic groups (pinteraction = 0.009). Our findings suggest that a plant-based diet rich in healthy plant foods might be associated with lower odds of NAFLD, particularly among US non-Hispanic whites. Clinical trials and cohort studies to validate our findings are needed.

The objective of this study was to investigate the effect of dietary fatty acid (FA) composition on bile acid (BA) metabolism in a pig model of NAFLD, by using a multiomics approach combined with histology and serum biochemistry. Thirty 20-day-old Iberian pigs pair-housed in pens were randomly assigned to receive 1 of 3 hypercaloric diets for 10 wk: 1) lard-enriched (LAR; n = 5 pens), 2) olive oil-enriched (OLI; n = 5), and 3) coconut oil-enriched (COC; n = 5). Animals were euthanized on week 10 after blood sampling, and liver, colon, and distal ileum (DI) were collected for histology, metabolomics, and transcriptomics. Data were analyzed by multivariate and univariate statistics. Compared with OLI and LAR, COC increased primary and secondary BAs in liver, plasma, and colon. In addition, both COC and OLI reduced circulating fibroblast growth factor 19, increased hepatic necrosis, composite lesion score, and liver enzymes in serum, and upregulated genes involved in hepatocyte proliferation and DNA repair. The severity of liver disease in COC and OLI pigs was associated with increased levels of phosphatidylcholines, medium-chain triacylglycerides, trimethylamine-N-oxide, and long-chain acylcarnitines in the liver, and the expression of profibrotic markers in DI, but not with changes in the composition or size of BA pool. In conclusion, our results indicate a role of dietary FAs in the regulation of BA metabolism and progression of NAFLD. Interventions that aim to modify the composition of dietary FAs, rather than to regulate BA metabolism or signaling, may be more effective in the treatment of NAFLD.NEW & NOTEWORTHY Bile acid homeostasis and signaling is disrupted in NAFLD and may play a central role in the development of the disease. However, there are no studies addressing the impact of diet on bile acid metabolism in patients with NAFLD. In juvenile Iberian pigs, we show that fatty acid composition in high-fat high-fructose diets affects BA levels in liver, plasma, and colon but these changes were not associated with the severity of the disease.